View source for Colorectal cancer

{{Short description|Cancer of the colon or rectum}}
{{About||cancer of the anus|Anal cancer}}
{{redirect|Intestinal cancer|cancer of the small intestine|Small intestine cancer}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Use mdy dates|date=December 2013}}
{{Infobox medical condition (new)
| synonyms      = {{hlist|Colon cancer|rectal cancer|bowel cancer}}
| image         = Blausen 0246 ColorectalCancer.png
| caption       = Location and appearance of two example colorectal tumors
| field         = [[Gastroenterology]] [[General surgery]] [[Oncology]]
| symptoms      = {{hlist|[[Blood in stool]]|change in bowel movements|unintentional [[weight loss]]|[[vomiting]]|fatigue<ref name=NCI2014Pt/>}}
| complications = 
| onset         = 
| duration      = 
| causes        = Lifestyle factors and genetic disorders<ref name=WCR2014_5.5/><ref name=NCI2014Pre/>
| risks         = {{hlist|Diet|[[obesity]]|smoking|lack of [[physical activity]]|[[alcohol and cancer|alcohol use]]<ref name=WCR2014_5.5/><ref name="Theodoratou2017"/>}}
| diagnosis     = [[Tissue biopsy]] during a [[sigmoidoscopy]] or [[colonoscopy]]<ref name=NCI2014Pt/>
| differential  = 
| prevention    = [[Cancer screening|Screening]] from age of 45 to 75
| treatment     = {{hlist|[[Surgery]]|[[radiation therapy]]|[[chemotherapy]]|[[targeted therapy]]<ref name=NCI2014PtTx/>}}
| medication    = 
| prognosis     = [[Five-year survival rate]] 65% (US)<ref name=SEER2014/>
| frequency     = 9.4 million (2015)<ref name=GBD2015Pre>{{cite journal | vauthors = Vos T, Barber RM, Bell B, Bertozzi-Villa A, Biryukov S, Bolliger I, etal | collaboration = GBD 2015 Disease and Injury Incidence and Prevalence Collaborators   | title = Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1545–1602 | date = October 2016 | pmid = 27733282 | pmc = 5055577 | doi = 10.1016/S0140-6736(16)31678-6 }}</ref>
| deaths        = 551,000 (2018)<ref name=Bray2018/>
| name          = 
}}
<!-- Definition and symptoms -->
'''Colorectal cancer''' ('''CRC'''), also known as '''bowel cancer''', '''colon cancer''', or '''rectal cancer''', is the development of [[cancer]] from the [[Colon (anatomy)|colon]] or [[rectum]] (parts of the [[large intestine]]).<ref name="NCI2014PtTx">{{cite web|title=Colon Cancer Treatment (PDQ®)|url=http://www.cancer.gov/cancertopics/pdq/treatment/colon/Patient/page1/AllPages|website=NCI|access-date=29 June 2014|date=2014-05-12|url-status=live|archive-url=https://web.archive.org/web/20140705111552/http://www.cancer.gov/cancertopics/pdq/treatment/colon/Patient/page1/AllPages|archive-date=July 5, 2014|df=mdy-all}}</ref> Signs and symptoms may include [[Lower gastrointestinal bleeding|blood in the stool]], a change in [[bowel movements]], weight loss, abdominal pain and fatigue.<ref>{{Cite web |title=Colorectal Cancer Signs and Symptoms {{!}} Signs of Colorectal Cancer |url=https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/signs-and-symptoms.html |access-date=2023-02-08 |website=www.cancer.org |language=en}}</ref> Most colorectal cancers are due to lifestyle factors and genetic disorders.<ref name="WCR2014_5.5" /><ref name="NCI2014Pre">{{cite web|title=Colorectal Cancer Prevention (PDQ®)|url=http://www.cancer.gov/cancertopics/pdq/prevention/colorectal/HealthProfessional/page1/AllPages|website=National Cancer Institute|access-date=29 June 2014|date=2014-02-27|url-status=live|archive-url=https://web.archive.org/web/20140705111841/http://www.cancer.gov/cancertopics/pdq/prevention/colorectal/HealthProfessional/page1/AllPages|archive-date=July 5, 2014|df=mdy-all}}</ref> Risk factors include diet, [[obesity]], smoking, and lack of [[physical activity]].<ref name="WCR2014_5.5">{{cite book | vauthors = Bosman FT | veditors = Stewart BW, Wild CP |title=World Cancer Report |date=2014 |publisher=the International Agency for Research on Cancer, World Health Organization |isbn=978-92-832-0443-5 |pages=392–402 |chapter-url=http://publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014 |chapter=Chapter 5.5: Colorectal Cancer}}</ref> Dietary factors that increase the risk include [[red meat]], [[processed meat]], and [[alcohol (drug)|alcohol]].<ref name="WCR2014_5.5" /><ref name="Theodoratou2017">{{cite journal | vauthors = Theodoratou E, Timofeeva M, Li X, Meng X, Ioannidis JP | title = Nature, Nurture, and Cancer Risks: Genetic and Nutritional Contributions to Cancer | journal = Annual Review of Nutrition | volume = 37 | pages = 293–320 | date = August 2017 | pmid = 28826375 | pmc = 6143166 | doi = 10.1146/annurev-nutr-071715-051004 | type = Review }}</ref> Another risk factor is [[inflammatory bowel disease]], which includes [[Crohn's disease]] and [[ulcerative colitis]].<ref name="WCR2014_5.5" /> Some of the inherited genetic disorders that can cause colorectal cancer include [[familial adenomatous polyposis]] and [[hereditary non-polyposis colon cancer]]; however, these represent less than 5% of cases.<ref name="WCR2014_5.5" /><ref name="NCI2014Pre" /> It typically starts as a [[adenoma|benign tumor]], often in the form of a [[colorectal polyp|polyp]], which over time becomes [[carcinoma|cancerous]].<ref name="WCR2014_5.5" />

<!-- Diagnosis, prevention and screening -->
Colorectal cancer may be diagnosed by [[Biopsy|obtaining a sample]] of the colon during a [[sigmoidoscopy]] or [[colonoscopy]].<ref name="NCI2014Pt">{{cite web |date=2014-05-12 |title=General Information About Colon Cancer |url=http://www.cancer.gov/cancertopics/pdq/treatment/colon/Patient |url-status=live |archive-url=https://web.archive.org/web/20140704182634/http://www.cancer.gov/cancertopics/pdq/treatment/colon/Patient |archive-date=July 4, 2014 |access-date=29 June 2014 |website=NCI |df=mdy-all}}</ref> This is then followed by [[medical imaging]] to determine whether the disease has spread.<ref name="NCI2014PtTx" /> [[Cancer screening|Screening]] is effective for preventing and decreasing deaths from colorectal cancer.<ref name="USPSTF2016" /> Screening, by one of a number of methods, is recommended starting from the age of 45 to 75. It was recommended starting at age 50 but it was changed to 45 due to increasing numbers of colon cancers.<ref name="USPSTF2016">{{cite journal | vauthors = Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW, García FA, Gillman MW, Harper DM, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Owens DK, Phillips WR, Phipps MG, Pignone MP, Siu AL | title = Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement | journal = JAMA | volume = 315 | issue = 23 | pages = 2564–2575 | date = June 2016 | pmid = 27304597 | doi = 10.1001/jama.2016.5989 | doi-access = free }}</ref><ref>{{Cite web |title=First Colonoscopies Now Recommended at Age 45 |url=https://thedacare.org/news-and-events/company-news/first-colonoscopies-now-recommended-at-age-45/ |access-date=2022-12-30 |website=ThedaCare |language=en-US}}</ref> During colonoscopy, small polyps may be removed if found.<ref name="WCR2014_5.5" /> If a large polyp or tumor is found, a [[biopsy]] may be performed to check if it is cancerous. [[Aspirin]] and other [[non-steroidal anti-inflammatory drugs]] decrease the risk of pain during polyp excision.<ref name="WCR2014_5.5" /><ref>{{cite journal | vauthors = Thorat MA, Cuzick J | title = Role of aspirin in cancer prevention | journal = Current Oncology Reports | volume = 15 | issue = 6 | pages = 533–540 | date = December 2013 | pmid = 24114189 | doi = 10.1007/s11912-013-0351-3 | s2cid = 40187047 | url = http://qmro.qmul.ac.uk/xmlui/handle/123456789/10490 }}</ref> Their general use is not recommended for this purpose, however, due to side effects.<ref>{{cite journal | vauthors =  | title = Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: recommendation statement | journal = American Family Physician | volume = 76 | issue = 1 | pages = 109–113 | date = July 2007 | pmid = 17668849 | url = http://www.aafp.org/afp/2007/0701/p109.html | url-status = live | df = mdy-all | archive-url = https://web.archive.org/web/20140714192923/http://www.aafp.org/afp/2007/0701/p109.html | archive-date = July 14, 2014 }}</ref>

<!-- Management, prognosis and epidemiology -->
Treatments used for colorectal cancer may include some combination of surgery, [[radiation therapy]], [[chemotherapy]], and [[targeted therapy]].<ref name=NCI2014PtTx/> Cancers that are confined within the wall of the colon may be curable with surgery, while [[Metastasis|cancer that has spread widely]] is usually not curable, with management being directed towards improving [[quality of life]] and symptoms.<ref name=NCI2014PtTx/> The [[five-year survival rate]] in the United States was around 65% in 2014.<ref name="SEER2014">{{cite web|title=SEER Stat Fact Sheets: Colon and Rectum Cancer|url=http://seer.cancer.gov/statfacts/html/colorect.html|website=NCI|access-date=18 June 2014|url-status=live|archive-url=https://web.archive.org/web/20140624140833/http://seer.cancer.gov/statfacts/html/colorect.html|archive-date=June 24, 2014|df=mdy-all}}</ref> The individual likelihood of survival depends on how advanced the cancer is, whether or not all the cancer can be removed with surgery, and the person's overall health.<ref name=NCI2014Pt/> Globally, colorectal cancer is the third most common type of cancer, making up about 10% of all cases.<ref name="WCR2014Epi">{{cite book | vauthors = Forman D, Ferlay J | veditors = Stewart BW, Wild CP |title=World Cancer Report |date=2014 |publisher=the International Agency for Research on Cancer, World Health Organization |isbn=978-92-832-0443-5 |pages=16–53 |chapter-url=http://publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014 |chapter=Chapter 1.1: The global and regional burden of cancer}}</ref> In 2018, there were 1.09 million new cases and 551,000 deaths from the disease.<ref name=Bray2018>{{cite journal | vauthors = Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A | title = Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries | journal = CA: A Cancer Journal for Clinicians | volume = 68 | issue = 6 | pages = 394–424 | date = November 2018 | pmid = 30207593 | doi = 10.3322/caac.21492 | s2cid = 52188256 | doi-access = free }}</ref> It is more common in [[Developed country|developed countries]], where more than 65% of cases are found.<ref name="WCR2014_5.5" /> It is less common in women than men.<ref name="WCR2014_5.5" />
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==Signs and symptoms==
The signs and symptoms of colorectal cancer depend on the location of the [[tumor]] in the [[bowel]], and whether it has spread elsewhere in the body ([[metastasis]]). The classic warning signs include: worsening [[constipation]], blood in the [[Stool test|stool]], decrease in stool caliber (thickness), loss of appetite, loss of weight, and [[nausea]] or [[vomiting]] in someone over 50 years old.<ref>{{cite book | vauthors = Alpers DH, Kalloo AN, Kaplowitz N, Owyang C, Powell DW | veditors = Yamada T |title=Principles of clinical gastroenterology |year=2008 |publisher=Wiley-Blackwell |location=Chichester, West Sussex |isbn=978-1-4051-6910-3 |pages=381 |url=https://books.google.com/books?id=Zo7QcUjz0PYC&pg=PA381 |url-status=live |archive-url=https://web.archive.org/web/20150928133221/https://books.google.com/books?id=Zo7QcUjz0PYC&pg=PA381 |archive-date=September 28, 2015 |df=mdy-all }}</ref> Around 50% of people who have colorectal cancer do not report any symptoms.<ref>{{cite journal | vauthors = Juul JS, Hornung N, Andersen B, Laurberg S, Olesen F, Vedsted P | title = The value of using the faecal immunochemical test in general practice on patients presenting with non-alarm symptoms of colorectal cancer | language = En | journal = British Journal of Cancer | volume = 119 | issue = 4 | pages = 471–479 | date = August 2018 | pmid = 30065255 | pmc = 6133998 | doi = 10.1038/s41416-018-0178-7 }}</ref>

[[Rectal bleeding]] or [[anemia]] are high-risk symptoms in people over the age of 50.<ref name="Sym11">{{cite journal | vauthors = Astin M, Griffin T, Neal RD, Rose P, Hamilton W | title = The diagnostic value of symptoms for colorectal cancer in primary care: a systematic review | journal = The British Journal of General Practice | volume = 61 | issue = 586 | pages = e231–e243 | date = May 2011 | pmid = 21619747 | pmc = 3080228 | doi = 10.3399/bjgp11X572427 }}</ref> Weight loss and changes in a person's bowel habit are typically only concerning if they are associated with rectal bleeding.<ref name="Sym11" /><ref name="pmid21624112">{{cite journal | vauthors = Adelstein BA, Macaskill P, Chan SF, Katelaris PH, Irwig L | title = Most bowel cancer symptoms do not indicate colorectal cancer and polyps: a systematic review | journal = BMC Gastroenterology | volume = 11 | pages = 65 | date = May 2011 | pmid = 21624112 | pmc = 3120795 | doi = 10.1186/1471-230X-11-65 | doi-access = free }}</ref>

==Cause==
75–95% of colorectal cancer cases occur in people with little or no genetic risk.<ref name="Cause11">{{cite journal | vauthors = Watson AJ, Collins PD | title = Colon cancer: a civilization disorder | journal = Digestive Diseases | volume = 29 | issue = 2 | pages = 222–228 | year = 2011 | pmid = 21734388 | doi = 10.1159/000323926 | s2cid = 7640363 | url = https://ueaeprints.uea.ac.uk/id/eprint/48949/1/Colon_Cancer_Falk_2010_PDC.docx }}</ref><ref name="Lancet10">{{cite journal | vauthors = Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N | title = Colorectal cancer | journal = Lancet | volume = 375 | issue = 9719 | pages = 1030–1047 | date = March 2010 | pmid = 20304247 | doi = 10.1016/S0140-6736(10)60353-4 | s2cid = 25299272 }}</ref> Risk factors include older age, male sex,<ref name=Lancet10/> high intake of fat, [[sugar]], [[alcohol (drug)|alcohol]], [[red meat]], [[processed meat]]s, [[obesity]], [[smoking]], and a lack of [[physical exercise]].<ref name=Cause11/><ref name="WCRF2011">{{Cite web|url=http://www.wcrf.org/sites/default/files/Colorectal-Cancer-2011-Report.pdf|title=Colorectal Cancer 2011 Report: Food, Nutrition, Physical Activity, and the Prevention of Colorectal Cancer|date=2011|publisher=World Cancer Research Fund & American Institute for Cancer Research|url-status=live|archive-url=https://web.archive.org/web/20160909084341/http://www.wcrf.org/sites/default/files/Colorectal-Cancer-2011-Report.pdf|archive-date=September 9, 2016|df=mdy-all}}</ref> The Rectal Cancer Survival Calculator developed by the [[MD Anderson Cancer Center]] additionally considers race to be a risk factor; however, there are equity issues concerning whether this might lead to inequity in clinical decision making.<ref>{{Cite journal |last1=Vyas |first1=Darshali A. |last2=Eisenstein |first2=Leo G. |last3=Jones |first3=David S. |date=2020-08-27 |editor-last=Malina |editor-first=Debra |title=Hidden in Plain Sight — Reconsidering the Use of Race Correction in Clinical Algorithms |journal=New England Journal of Medicine |language=en |volume=383 |issue=9 |pages=874–882 |doi=10.1056/NEJMms2004740 |pmid=32853499 |s2cid=221359557 |issn=0028-4793|doi-access=free }}</ref><ref>{{Cite journal |last1=Bowles |first1=Tawnya L. |last2=Hu |first2=Chung-Yuan |last3=You |first3=Nancy Y. |last4=Skibber |first4=John M. |last5=Rodriguez-Bigas |first5=Miguel A. |last6=Chang |first6=George J. |date=May 2013 |title=An Individualized Conditional Survival Calculator for Patients with Rectal Cancer |url=https://journals.lww.com/00003453-201305000-00003 |journal=Diseases of the Colon & Rectum |language=en |volume=56 |issue=5 |pages=551–559 |doi=10.1097/DCR.0b013e31827bd287 |issn=0012-3706 |pmc=3673550 |pmid=23575393}}</ref> Approximately 10% of cases are linked to insufficient activity.<ref>{{cite journal | vauthors = Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT | title = Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy | journal = Lancet | volume = 380 | issue = 9838 | pages = 219–229 | date = July 2012 | pmid = 22818936 | pmc = 3645500 | doi = 10.1016/S0140-6736(12)61031-9 }}</ref> The risk from alcohol appears to increase at greater than one drink per day.<ref name="Fedirko2011">{{cite journal | vauthors = Fedirko V, Tramacere I, Bagnardi V, Rota M, Scotti L, Islami F, Negri E, Straif K, Romieu I, La Vecchia C, Boffetta P, Jenab M | title = Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies | journal = Annals of Oncology | volume = 22 | issue = 9 | pages = 1958–1972 | date = September 2011 | pmid = 21307158 | doi = 10.1093/annonc/mdq653 | doi-access = free }}</ref> Drinking five glasses of water a day is linked to a decrease in the risk of colorectal cancer and [[adenomatous]] polyps.<ref>{{cite journal | vauthors = Valtin H | title = "Drink at least eight glasses of water a day." Really? Is there scientific evidence for "8 x 8"? | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 283 | issue = 5 | pages = R993–1004 | date = November 2002 | pmid = 12376390 | doi = 10.1152/ajpregu.00365.2002 | s2cid = 2256436 }}</ref> ''[[Streptococcus gallolyticus]]'' is associated with colorectal cancer.<ref name="BoleijvanGelder2011">{{cite journal | vauthors = Boleij A, van Gelder MM, Swinkels DW, Tjalsma H | title = Clinical Importance of Streptococcus gallolyticus infection among colorectal cancer patients: systematic review and meta-analysis | journal = Clinical Infectious Diseases | volume = 53 | issue = 9 | pages = 870–878 | date = November 2011 | pmid = 21960713 | doi = 10.1093/cid/cir609 | doi-access = free }}</ref> Some strains of ''Streptococcus bovis/Streptococcus equinus'' complex are consumed by millions of people daily and thus may be safe.<ref name="JansMeile2015">{{cite journal | vauthors = Jans C, Meile L, Lacroix C, Stevens MJ | title = Genomics, evolution, and molecular epidemiology of the Streptococcus bovis/Streptococcus equinus complex (SBSEC) | journal = Infection, Genetics and Evolution | volume = 33 | pages = 419–436 | date = July 2015 | pmid = 25233845 | doi = 10.1016/j.meegid.2014.09.017 | bibcode = 2015InfGE..33..419J }}</ref> 25 to 80% of people with ''Streptococcus bovis/gallolyticus'' bacteremia have concomitant colorectal tumors.<ref name="AbdulamirHafidh2011">{{cite journal | vauthors = Abdulamir AS, Hafidh RR, Abu Bakar F | title = The association of Streptococcus bovis/gallolyticus with colorectal tumors: the nature and the underlying mechanisms of its etiological role | journal = Journal of Experimental & Clinical Cancer Research | volume = 30 | issue = 1 | pages = 11 | date = January 2011 | pmid = 21247505 | pmc = 3032743 | doi = 10.1186/1756-9966-30-11 | doi-access = free }}{{CC-notice|cc=by2|url=https://jeccr.biomedcentral.com/articles/10.1186/1756-9966-30-11|author(s)=Ahmed S Abdulamir, Rand R Hafidh, and Fatimah Abu Bakar}}</ref> Seroprevalence of ''Streptococcus bovis/gallolyticus'' is considered as a candidate practical marker for the early prediction of an underlying bowel lesion at high risk population.<ref name=AbdulamirHafidh2011/> It has been suggested that the presence of antibodies to ''Streptococcus bovis/gallolyticus'' antigens or the antigens themselves in the bloodstream may act as markers for the carcinogenesis in the colon.<ref name=AbdulamirHafidh2011/>

[[Pathogenic Escherichia coli|Pathogenic ''Escherichia coli'']] may increase the risk of colorectal cancer by producing the [[Genotoxicity|genotoxic]] [[metabolite]], [[colibactin]].<ref name="pmid32317778">{{cite journal | vauthors = Arthur JC | title = Microbiota and colorectal cancer: colibactin makes its mark | journal = Nature Reviews. Gastroenterology & Hepatology | volume = 17 | issue = 6 | pages = 317–318 | date = June 2020 | pmid = 32317778 | doi = 10.1038/s41575-020-0303-y | s2cid = 216033220 }}</ref>

===Inflammatory bowel disease===
People with [[inflammatory bowel disease]] ([[ulcerative colitis]] and [[Crohn's disease]]) are at increased risk of colon cancer.<ref name="IBD11">{{Cite book | vauthors = Jawad N, Direkze N, Leedham SJ | chapter = Inflammatory Bowel Disease and Colon Cancer | title = Inflammation and Gastrointestinal Cancers | journal = <!-- Disable Citation bot --> | volume = 185 | pages = 99–115 | year = 2011 | pmid = 21822822 | doi = 10.1007/978-3-642-03503-6_6 | series = Recent Results in Cancer Research | isbn = 978-3-642-03502-9 }}</ref><ref name="pmid26004415">{{cite journal | vauthors = Hu T, Li LF, Shen J, Zhang L, Cho CH | title = Chronic inflammation and colorectal cancer: the role of vascular endothelial growth factor | journal = Current Pharmaceutical Design | volume = 21 | issue = 21 | pages = 2960–2967 | date = 2015 | pmid = 26004415 | doi = 10.2174/1381612821666150514104244 }}</ref> The risk increases the longer a person has the disease, and the worse the severity of inflammation.<ref name="IBD09">{{cite journal | vauthors = Triantafillidis JK, Nasioulas G, Kosmidis PA | title = Colorectal cancer and inflammatory bowel disease: epidemiology, risk factors, mechanisms of carcinogenesis and prevention strategies | journal = Anticancer Research | volume = 29 | issue = 7 | pages = 2727–2737 | date = July 2009 | pmid = 19596953 }}</ref> In these high risk groups, both prevention with [[aspirin]] and regular [[colonoscopies]] are recommended.<ref name="Bye-2017">{{cite journal | vauthors = Bye WA, Nguyen TM, Parker CE, Jairath V, East JE | title = Strategies for detecting colon cancer in patients with inflammatory bowel disease | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | pages = CD000279 | date = September 2017 | issue = 9 | pmid = 28922695 | pmc = 6483622 | doi = 10.1002/14651858.cd000279.pub4 }}</ref> [[Endoscopic]] surveillance in this high-risk population may reduce the development of colorectal cancer through early diagnosis and may also reduce the chances of dying from colon cancer.<ref name="Bye-2017" /> People with inflammatory bowel disease account for less than 2% of colon cancer cases yearly.<ref name=IBD09/> In those with Crohn's disease, 2% get colorectal cancer after 10&nbsp;years, 8% after 20&nbsp;years, and 18% after&nbsp;30 years.<ref name=IBD09/> In people who have ulcerative colitis, approximately 16% develop either a [[dysplasia|cancer precursor]] or cancer of the colon over 30&nbsp;years.<ref name=IBD09/>

===Genetics===
Those with a family history in two or more [[Degree of relationship|first-degree relatives]] (such as a parent or sibling) have a two to threefold greater risk of disease, and this group accounts for about 20% of all cases.<!--<ref name=Lancet10/>--> A number of genetic syndromes are also associated with higher rates of colorectal cancer. The most common of these is [[hereditary nonpolyposis colorectal cancer]] (HNPCC, or Lynch syndrome) which is present in about 3% of people with colorectal cancer.<ref name=Lancet10/> Other syndromes that are strongly associated with colorectal cancer include [[Gardner syndrome]] and [[familial adenomatous polyposis]] (FAP).<ref name="pmid20141232">{{cite journal | vauthors = Juhn E, Khachemoune A | title = Gardner syndrome: skin manifestations, differential diagnosis and management | journal = American Journal of Clinical Dermatology | volume = 11 | issue = 2 | pages = 117–122 | date = 2010 | pmid = 20141232 | doi = 10.2165/11311180-000000000-00000 | s2cid = 36836169 }}</ref> For people with these syndromes, cancer almost always occurs and makes up 1% of the cancer cases.<ref name="pmid19822006">{{cite journal | vauthors = Half E, Bercovich D, Rozen P | title = Familial adenomatous polyposis | journal = Orphanet Journal of Rare Diseases | volume = 4 | pages = 22 | date = October 2009 | pmid = 19822006 | pmc = 2772987 | doi = 10.1186/1750-1172-4-22 | doi-access = free }}</ref> A total [[proctocolectomy]] may be recommended for people with FAP as a preventive measure due to the high risk of malignancy. Colectomy, removal of the colon, may not suffice as a preventive measure because of the high risk of rectal cancer if the rectum remains.<ref>{{cite journal | vauthors = Möslein G, Pistorius S, Saeger HD, Schackert HK | title = Preventive surgery for colon cancer in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer syndrome | journal = Langenbeck's Archives of Surgery | volume = 388 | issue = 1 | pages = 9–16 | date = March 2003 | pmid = 12690475 | doi = 10.1007/s00423-003-0364-8 | s2cid = 21385340 }}</ref> The most common polyposis syndrome affecting the colon is [[serrated polyposis syndrome]],<ref name=Mankaney>{{cite journal | vauthors = Mankaney G, Rouphael C, Burke CA | title = Serrated Polyposis Syndrome | journal = Clinical Gastroenterology and Hepatology | volume = 18 | issue = 4 | pages = 777–779 | date = April 2020 | pmid = 31520728 | doi = 10.1016/j.cgh.2019.09.006 | doi-access = free }}</ref> which is associated with a 25-40% risk of CRC.<ref name=Fan>{{cite journal | vauthors = Fan C, Younis A, Bookhout CE, Crockett SD | title = Management of Serrated Polyps of the Colon | journal = Current Treatment Options in Gastroenterology | volume = 16 | issue = 1 | pages = 182–202 | date = March 2018 | pmid = 29445907 | pmc = 6284520 | doi = 10.1007/s11938-018-0176-0 }}</ref>

Mutations in the pair of genes ([[DNA polymerase epsilon|POLE]] and [[POLD1]]) have been associated with familial colon cancer.<ref name=Bourdais2017>{{cite journal | vauthors = Bourdais R, Rousseau B, Pujals A, Boussion H, Joly C, Guillemin A, Baumgaertner I, Neuzillet C, Tournigand C | title = Polymerase proofreading domain mutations: New opportunities for immunotherapy in hypermutated colorectal cancer beyond MMR deficiency | journal = Critical Reviews in Oncology/Hematology | volume = 113 | pages = 242–248 | date = May 2017 | pmid = 28427513 | doi = 10.1016/j.critrevonc.2017.03.027 }}</ref>

Most deaths due to colon cancer are associated with metastatic disease. A gene that appears to contribute to the potential for metastatic disease, metastasis associated in colon cancer 1 (''MACC1''), has been isolated.<ref name="Stein2009">{{cite journal | vauthors = Stein U, Walther W, Arlt F, Schwabe H, Smith J, Fichtner I, Birchmeier W, Schlag PM | title = MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis | journal = Nature Medicine | volume = 15 | issue = 1 | pages = 59–67 | date = January 2009 | pmid = 19098908 | doi = 10.1038/nm.1889 | s2cid = 8854895 }}</ref> It is a [[transcriptional]] factor that influences the expression of [[hepatocyte growth factor]]. This gene is associated with the proliferation, invasion, and scattering of colon cancer cells in [[cell culture]], and tumor growth and metastasis in mice. MACC1 may be a potential target for cancer intervention, but this possibility needs to be confirmed with clinical studies.<ref name=Stein2013>Stein U (2013) MACC1 – a novel target for solid cancers. Expert Opin Ther Targets</ref>

[[Epigenetic]] factors, such as abnormal [[DNA methylation]] of [[tumor suppressor]] promoters, play a role in the development of colorectal cancer.<ref>{{cite journal | vauthors = Schuebel KE, Chen W, Cope L, Glöckner SC, Suzuki H, Yi JM, Chan TA, Van Neste L, Van Criekinge W, van den Bosch S, van Engeland M, Ting AH, Jair K, Yu W, Toyota M, Imai K, Ahuja N, Herman JG, Baylin SB | title = Comparing the DNA hypermethylome with gene mutations in human colorectal cancer | journal = PLOS Genetics | volume = 3 | issue = 9 | pages = 1709–1723 | date = September 2007 | pmid = 17892325 | pmc = 1988850 | doi = 10.1371/journal.pgen.0030157 | author-link16 = Kohzoh Imai | author-link17 = Nita Ahuja | df = mdy-all | author-link18 = James G. Herman | author-link19 = Stephen B. Baylin | doi-access = free }}</ref>

[[Ashkenazi Jews]] have a 6% higher risk rate of getting [[adenoma]]s and then colon cancer due to mutations in the [[APC gene]] being more common.<ref>{{cite web |title=What is the relationship between Ashkenazi Jews and colorectal cancer? |url=https://www.webmd.com/colorectal-cancer/qa/what-is-the-relationship-between-ashkenazi-jews-and-colorectal-cancer |website=WebMD |access-date=17 October 2019 |language=en}}</ref>

==Pathogenesis==
Colorectal cancer is a disease originating from the [[epithelium|epithelial cells]] lining the colon or rectum of the [[Human gastrointestinal tract|gastrointestinal tract]], most frequently as a result of genetic mutations in the [[Wnt signaling pathway]] that increases signaling activity.<ref name="Tabibzadeh-2020">{{Cite journal |last1=Tabibzadeh |first1=Alireza |last2=Tameshkel |first2=Fahimeh Safarnezhad |last3=Moradi |first3=Yousef |last4=Soltani |first4=Saber |last5=Moradi-Lakeh |first5=Maziar |last6=Ashrafi |first6=G. Hossein |last7=Motamed |first7=Nima |last8=Zamani |first8=Farhad |last9=Motevalian |first9=Seyed Abbas |last10=Panahi |first10=Mahshid |last11=Esghaei |first11=Maryam |last12=Ajdarkosh |first12=Hossein |last13=Mousavi-Jarrahi |first13=Alireza |last14=Niya |first14=Mohammad Hadi Karbalaie |date=2020-10-30 |title=Signal transduction pathway mutations in gastrointestinal (GI) cancers: a systematic review and meta-analysis |journal=Scientific Reports |volume=10 |issue=1 |pages=18713 |doi=10.1038/s41598-020-73770-1 |issn=2045-2322 |pmc=7599243 |pmid=33127962|bibcode=2020NatSR..1018713T }}</ref> The Wnt signaling pathway normally plays an important role for normal function of these cells including maintaining this lining. Mutations can be [[Hereditary disease|inherited]] or [[somatic cell|acquired]], and most probably occur in the [[intestinal crypt]] [[stem cell]].<ref>{{cite journal | vauthors = Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M | title = Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis | journal = Nature | volume = 363 | issue = 6429 | pages = 558–561 | date = June 1993 | pmid = 8505985 | doi = 10.1038/363558a0 | s2cid = 4254940 | bibcode = 1993Natur.363..558I }}</ref><ref>{{cite journal | vauthors = Chakravarthi S, Krishnan B, Madhavan M | title = Apoptosis and expression of p53 in colorectal neoplasms | journal = Indian J. Med. Res. | volume = 86 | issue = 7 | pages = 95–102 | year = 1999 }}</ref><ref>{{cite journal | vauthors = Abdul Khalek FJ, Gallicano GI, Mishra L | title = Colon cancer stem cells | journal = Gastrointestinal Cancer Research | issue = Suppl 1 | pages = S16–S23 | date = November 2010 | pmid = 21472043 | pmc = 3047031 }}</ref> The most commonly mutated gene in all colorectal cancer is the ''[[Adenomatous polyposis coli|APC]]'' gene, which produces the APC protein.<ref name="Tabibzadeh-2020" /> The APC protein prevents the accumulation of [[β-catenin]] protein. Without APC, [[β-catenin]] accumulates to high levels and translocates (moves) into the [[Cell nucleus|nucleus]], binds to DNA, and activates the [[transcription (genetics)|transcription]] of proto-[[oncogenes]]. These genes are normally important for stem cell renewal and differentiation, but when inappropriately expressed at high levels, they can cause cancer.<ref name="Tabibzadeh-2020" /> While APC is mutated in most colon cancers, some cancers have increased β-catenin because of mutations in β-catenin (CTNNB1) that block its own breakdown, or have mutations in other genes with function similar to APC such as [[AXIN1]], [[AXIN2]], [[TCF7L2]], or [[Naked cuticle 1|NKD1]].<ref name="markowitz">{{cite journal | vauthors = Markowitz SD, Bertagnolli MM | title = Molecular origins of cancer: Molecular basis of colorectal cancer | journal = The New England Journal of Medicine | volume = 361 | issue = 25 | pages = 2449–2460 | date = December 2009 | pmid = 20018966 | pmc = 2843693 | doi = 10.1056/NEJMra0804588 }}</ref>

Beyond the defects in the [[Wnt signaling pathway]], other mutations must occur for the cell to become cancerous. The [[p53]] protein, produced by the ''TP53'' gene, normally monitors [[cell division]] and induces their [[apoptosis|programmed death]] if they have Wnt pathway defects. Eventually, a [[cell line]] acquires a mutation in the ''TP53'' gene and transforms the tissue from a [[adenoma|benign epithelial tumor]] into an invasive [[carcinoma|epithelial cell cancer]]. Sometimes the gene encoding p53 is not mutated, but another protective protein named [[BAX (gene)|BAX]] is mutated instead.<ref name="markowitz"/>

Other proteins responsible for programmed cell death that are commonly deactivated in colorectal cancers are [[TGF-β]] and DCC ([[Deleted in Colorectal Cancer]]). TGF-β has a deactivating mutation in at least half of colorectal cancers. Sometimes TGF-β is not deactivated, but a downstream protein named [[SMAD (protein)|SMAD]] is deactivated.<ref name="markowitz"/> DCC commonly has a deleted segment of a chromosome in colorectal cancer.<ref>{{cite journal | vauthors = Mehlen P, Fearon ER | title = Role of the dependence receptor DCC in colorectal cancer pathogenesis | journal = Journal of Clinical Oncology | volume = 22 | issue = 16 | pages = 3420–3428 | date = August 2004 | pmid = 15310786 | doi = 10.1200/JCO.2004.02.019 }}</ref>

Approximately 70% of all [[human gene]]s are expressed in colorectal cancer, with just over 1% of having increased expression in colorectal cancer compared to other forms of cancer.<ref name="Uh2017"/> Some genes are [[oncogenes]]: they are overexpressed in colorectal cancer. For example, genes encoding the proteins [[KRAS]], [[C-Raf|RAF]], and [[PI3K]], which normally stimulate the [[Cell cycle|cell to divide]] in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important. If a previous APC mutation occurred, a primary KRAS mutation often progresses to cancer rather than a self-limiting [[hyperplastic]] or borderline lesion.<ref>{{cite journal | vauthors = Vogelstein B, Kinzler KW | title = Cancer genes and the pathways they control | journal = Nature Medicine | volume = 10 | issue = 8 | pages = 789–799 | date = August 2004 | pmid = 15286780 | doi = 10.1038/nm1087 | s2cid = 205383514 }}</ref> [[PTEN (gene)|PTEN]], a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated.<ref name="markowitz"/>

Comprehensive, [[genome]]-scale analysis has revealed that colorectal carcinomas can be categorized into hypermutated and non-hypermutated tumor types.<ref name="Muzny-2012">{{cite journal | vauthors = Muzny DM, Bainbridge MN, Chang K, Dinh HH, Drummond JA, Fowler G, etal | collaboration = Cancer Genome Atlas Network | title = Comprehensive molecular characterization of human colon and rectal cancer | journal = Nature | volume = 487 | issue = 7407 | pages = 330–337 | date = July 2012 | pmid = 22810696 | pmc = 3401966 | doi = 10.1038/nature11252 | bibcode = 2012Natur.487..330T }}</ref> In addition to the oncogenic and inactivating mutations described for the genes above, non-hypermutated samples also contain mutated [[CTNNB1]], [[FAM123B]], [[SOX9]], [[Ataxia telangiectasia mutated|ATM]], and [[ARID1A]]. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of [[ACVR2A]], [[TGFBR2]], [[MSH3]], [[MSH6]], SLC9A9, [[TCF7L2]], and [[BRAF (gene)|BRAF]]. The common theme among these genes, across both tumor types, is their involvement in Wnt and TGF-β signaling pathways, which results in increased activity of [[MYC]], a central player in colorectal cancer.<ref name="Muzny-2012"/>

[[DNA mismatch repair|Mismatch repair]] (MMR) deficient tumours are characterized by a relatively high number of poly-nucleotide [[tandem repeat]]s.<ref>{{cite journal | vauthors = Gatalica Z, Vranic S, Xiu J, Swensen J, Reddy S | title = High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of personalized medicine | journal = Familial Cancer | volume = 15 | issue = 3 | pages = 405–412 | date = July 2016 | pmid = 26875156 | pmc = 4901118 | doi = 10.1007/s10689-016-9884-6 }}</ref> This is caused by a deficiency in MMR proteins – which are typically caused by [[Epigenetics|epigenetic]] silencing and or inherited mutations (''e.g.'', [[Hereditary nonpolyposis colorectal cancer|Lynch syndrome]]).<ref name="Ryan-2017">{{cite journal | vauthors = Ryan E, Sheahan K, Creavin B, Mohan HM, Winter DC | title = The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing | journal = Critical Reviews in Oncology/Hematology | volume = 116 | pages = 38–57 | date = August 2017 | pmid = 28693799 | doi = 10.1016/j.critrevonc.2017.05.006 }}</ref> 15 to 18 percent of colorectal cancer tumours have MMR deficiencies, with 3 percent developing due to Lynch syndrome.<ref>{{cite journal | vauthors = Hissong E, Crowe EP, Yantiss RK, Chen YT | title = Assessing colorectal cancer mismatch repair status in the modern era: a survey of current practices and re-evaluation of the role of microsatellite instability testing | journal = Modern Pathology | volume = 31 | issue = 11 | pages = 1756–1766 | date = November 2018 | pmid = 29955148 | doi = 10.1038/s41379-018-0094-7 | doi-access = free }}</ref> The role of the mismatch repair system is to protect the integrity of the genetic material within cells (''i.e.'', error detecting and correcting).<ref name="Ryan-2017" /> Consequently, a deficiency in MMR proteins may lead to an inability to detect and repair genetic damage, allowing for further cancer-causing mutations to occur and colorectal cancer to progress.<ref name="Ryan-2017" />

The polyp to cancer progression sequence is the classical model of colorectal cancer [[pathogenesis]].<ref name="Grady-2015">{{cite journal | vauthors = Grady WM, Markowitz SD | title = The molecular pathogenesis of colorectal cancer and its potential application to colorectal cancer screening | journal = Digestive Diseases and Sciences | volume = 60 | issue = 3 | pages = 762–772 | date = March 2015 | pmid = 25492499 | pmc = 4779895 | doi = 10.1007/s10620-014-3444-4 }}</ref> In this '''adenoma-carcinoma sequence''',<ref>{{Cite journal |last1=Leslie |first1=A. |last2=Carey |first2=F. A. |last3=Pratt |first3=N. R. |last4=Steele |first4=R. J. C. |date=July 2002 |title=The colorectal adenoma-carcinoma sequence |journal=The British Journal of Surgery |volume=89 |issue=7 |pages=845–860 |doi=10.1046/j.1365-2168.2002.02120.x |issn=0007-1323 |pmid=12081733|s2cid=36456541 |doi-access=free }}</ref> normal epithelial cells progress to [[dysplastic]] cells such as [[adenoma]]s, and then to carcinoma, by a process of progressive genetic mutation.<ref>{{Cite journal |last1=Nguyen |first1=Long H. |last2=Goel |first2=Ajay |last3=Chung |first3=Daniel C. |date=January 2020 |title=Pathways of Colorectal Carcinogenesis |journal=Gastroenterology |volume=158 |issue=2 |pages=291–302 |doi=10.1053/j.gastro.2019.08.059 |issn=0016-5085 |pmc=6981255 |pmid=31622622}}</ref> Central to the polyp to CRC sequence are gene mutations, epigenetic alterations, and local inflammatory changes.<ref name="Grady-2015" /> The polyp to CRC sequence can be used as an underlying framework to illustrate how specific molecular changes lead to various cancer subtypes.<ref name="Grady-2015" />

===Field defects===
[[File:Image of resected colon segment with cancer & 4 nearby polyps plus schematic of field defects with sub-clones.jpg|thumb|Longitudinally opened freshly resected colon segment showing a cancer and four polyps. Plus a schematic diagram indicating a likely field defect (a region of tissue that precedes and predisposes to the development of cancer) in this colon segment. The diagram indicates sub-clones and sub-sub-clones that were precursors to the tumors.]]

The term "field cancerization" was first used in 1953 to describe an area or "field" of epithelium that has been preconditioned (by what were largely unknown processes at the time) to predispose it towards development of cancer.<ref>{{cite journal | vauthors = Slaughter DP, Southwick HW, Smejkal W | title = Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin | journal = Cancer | volume = 6 | issue = 5 | pages = 963–968 | date = September 1953 | pmid = 13094644 | doi = 10.1002/1097-0142(195309)6:5<963::AID-CNCR2820060515>3.0.CO;2-Q | s2cid = 6736946 | doi-access = free }}</ref> Since then, the terms "field cancerization", "field carcinogenesis", "field defect", and "[[Immersed Boundary Method|field effect]]" have been used to describe pre-malignant or pre-neoplastic tissue in which new cancers are likely to arise.<ref>{{cite journal | vauthors = Giovannucci E, Ogino S | title = DNA methylation, field effects, and colorectal cancer | journal = Journal of the National Cancer Institute | volume = 97 | issue = 18 | pages = 1317–1319 | date = September 2005 | pmid = 16174847 | doi = 10.1093/jnci/dji305 | doi-access = free }}</ref>

Field defects are important in progression to colon cancer.<ref>{{cite journal | vauthors = Bernstein C, Bernstein H, Payne CM, Dvorak K, Garewal H | title = Field defects in progression to gastrointestinal tract cancers | journal = Cancer Letters | volume = 260 | issue = 1–2 | pages = 1–10 | date = February 2008 | pmid = 18164807 | pmc = 2744582 | doi = 10.1016/j.canlet.2007.11.027 }}</ref><ref>{{cite journal | vauthors = Nguyen H, Loustaunau C, Facista A, Ramsey L, Hassounah N, Taylor H, Krouse R, Payne CM, Tsikitis VL, Goldschmid S, Banerjee B, Perini RF, Bernstein C | title = Deficient Pms2, ERCC1, Ku86, CcOI in field defects during progression to colon cancer | journal = Journal of Visualized Experiments | issue = 41 | pages = 1931 | date = July 2010 | pmid = 20689513 | pmc = 3149991 | doi = 10.3791/1931 }} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149991/ 28 minute video]</ref>

However, as pointed out by Rubin, "The vast majority of studies in cancer research has been done on well-defined tumors ''in vivo'', or on discrete neoplastic foci ''in vitro''. Yet there is evidence that more than 80% of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion."<ref>{{cite journal | vauthors = Rubin H | title = Fields and field cancerization: the preneoplastic origins of cancer: asymptomatic hyperplastic fields are precursors of neoplasia, and their progression to tumors can be tracked by saturation density in culture | journal = BioEssays | volume = 33 | issue = 3 | pages = 224–231 | date = March 2011 | pmid = 21254148 | doi = 10.1002/bies.201000067 | s2cid = 44981539 }}</ref><ref>{{cite journal | vauthors = Tsao JL, Yatabe Y, Salovaara R, Järvinen HJ, Mecklin JP, Aaltonen LA, Tavaré S, Shibata D | title = Genetic reconstruction of individual colorectal tumor histories | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 3 | pages = 1236–1241 | date = February 2000 | pmid = 10655514 | pmc = 15581 | doi = 10.1073/pnas.97.3.1236 | doi-access = free | bibcode = 2000PNAS...97.1236T }}</ref> Similarly, Vogelstein et al.<ref name=Vogelstein /> pointed out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells. Likewise, epigenetic alterations present in tumors may have occurred in pre-neoplastic field defects.<ref name="Bernstein-2013">{{cite journal | vauthors = Bernstein C, Nfonsam V, Prasad AR, Bernstein H | title = Epigenetic field defects in progression to cancer | journal = World Journal of Gastrointestinal Oncology | volume = 5 | issue = 3 | pages = 43–49 | date = March 2013 | pmid = 23671730 | pmc = 3648662 | doi = 10.4251/wjgo.v5.i3.43 | doi-access = free }}</ref>

An expanded view of field effect has been termed "etiologic field effect", which encompasses not only molecular and pathologic changes in pre-neoplastic cells but also influences of exogenous environmental factors and molecular changes in the local [[Tumor microenvironment|microenvironment]] on neoplastic evolution from tumor initiation to death.<ref>{{cite journal | vauthors = Lochhead P, Chan AT, Nishihara R, Fuchs CS, Beck AH, Giovannucci E, Ogino S | title = Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression | journal = Modern Pathology | volume = 28 | issue = 1 | pages = 14–29 | date = January 2015 | pmid = 24925058 | pmc = 4265316 | doi = 10.1038/modpathol.2014.81 }}</ref>

===Epigenetics===
[[Epigenetics|Epigenetic]] alterations are much more frequent in colon cancer than genetic (mutational) alterations. As described by Vogelstein et al.,<ref name="Vogelstein">{{cite journal | vauthors = Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW | title = Cancer genome landscapes | journal = Science | volume = 339 | issue = 6127 | pages = 1546–1558 | date = March 2013 | pmid = 23539594 | pmc = 3749880 | doi = 10.1126/science.1235122 | bibcode = 2013Sci...339.1546V }}</ref> an average cancer of the colon has only 1 or 2 oncogene mutations and 1 to 5 tumor suppressor mutations (together designated "driver mutations"), with about 60 further "passenger" mutations. The oncogenes and tumor suppressor genes are well studied and are described above under [[#Pathogenesis|Pathogenesis]].<ref>{{cite book | veditors  = Wilbur B |title = The World of the Cell | edition = 7th | location = San Francisco, C | year = 2009 }}</ref><ref>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/O/Oncogenes.html Kimball's Biology Pages.] {{Webarchive|url=https://web.archive.org/web/20171231184143/http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/O/Oncogenes.html |date=December 31, 2017 }} "Oncogenes" Free full text</ref>

In addition to epigenetic alteration of expression of miRNAs, other common types of epigenetic alterations in cancers that change gene expression levels include direct hypermethylation or hypomethylation of CpG islands of protein-encoding genes and alterations in histones and chromosomal architecture that influence gene expression.<ref>{{cite journal | vauthors = Kanwal R, Gupta S | title = Epigenetic modifications in cancer | journal = Clinical Genetics | volume = 81 | issue = 4 | pages = 303–311 | date = April 2012 | pmid = 22082348 | pmc = 3590802 | doi = 10.1111/j.1399-0004.2011.01809.x }}</ref> As an example, 147 hypermethylations and 27 hypomethylations of protein coding genes were frequently associated with colorectal cancers. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers, and many others were hypermethylated in more than 50% of colon cancers.<ref name="Sch">{{cite journal | vauthors = Schnekenburger M, Diederich M | title = Epigenetics Offer New Horizons for Colorectal Cancer Prevention | journal = Current Colorectal Cancer Reports | volume = 8 | issue = 1 | pages = 66–81 | date = March 2012 | pmid = 22389639 | pmc = 3277709 | doi = 10.1007/s11888-011-0116-z }}</ref> In addition, 11 hypermethylations and 96 hypomethylations of miRNAs were also associated with colorectal cancers.<ref name=Sch /> Abnormal (aberrant) [[methylation]] occurs as a normal consequence of normal aging and the risk of colorectal cancer increases as a person gets older.<ref name="Epigenetics">{{cite journal | vauthors = Lao VV, Grady WM | title = Epigenetics and colorectal cancer | journal = Nature Reviews. Gastroenterology & Hepatology | volume = 8 | issue = 12 | pages = 686–700 | date = October 2011 | pmid = 22009203 | pmc = 3391545 | doi = 10.1038/nrgastro.2011.173 }}</ref> The source and trigger of this age-related methylation is unknown.<ref name="Epigenetics" /><ref>{{cite journal | vauthors = Klutstein M, Nejman D, Greenfield R, Cedar H | title = DNA Methylation in Cancer and Aging | journal = Cancer Research | volume = 76 | issue = 12 | pages = 3446–3450 | date = June 2016 | pmid = 27256564 | doi = 10.1158/0008-5472.CAN-15-3278 | doi-access = free }}</ref> Approximately half of the genes that show age-related methylation changes are the same genes that have been identified to be involved in the development of colorectal cancer.<ref name="Epigenetics" /> These findings may suggest a reason for age being associated with the increased risk of developing colorectal cancer.<ref name="Epigenetics" />

Epigenetic reductions of DNA repair enzyme expression may likely lead to the genomic and epigenomic instability characteristic of cancer.<ref>{{cite journal | vauthors = Jacinto FV, Esteller M | title = Mutator pathways unleashed by epigenetic silencing in human cancer | journal = Mutagenesis | volume = 22 | issue = 4 | pages = 247–253 | date = July 2007 | pmid = 17412712 | doi = 10.1093/mutage/gem009 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lahtz C, Pfeifer GP | title = Epigenetic changes of DNA repair genes in cancer | journal = Journal of Molecular Cell Biology | volume = 3 | issue = 1 | pages = 51–58 | date = February 2011 | pmid = 21278452 | pmc = 3030973 | doi = 10.1093/jmcb/mjq053 }}</ref><ref name="Bernstein-2013"/> As summarized in the articles [[Carcinogenesis]] and [[Neoplasm]], for sporadic cancers in general, a deficiency in DNA repair is occasionally due to a mutation in a DNA repair gene, but is much more frequently due to epigenetic alterations that reduce or silence expression of DNA repair genes.<ref>{{cite web |url=https://www.lecturio.com/concepts/colorectal-cancer/| title=Colorectal Cancer
|website=The Lecturio Medical Concept Library |access-date= 22 July 2021}}</ref>

Epigenetic alterations involved in the development of colorectal cancer may affect a person's response to chemotherapy.<ref>{{cite journal | vauthors = Coppedè F, Lopomo A, Spisni R, Migliore L | title = Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer | journal = World Journal of Gastroenterology | volume = 20 | issue = 4 | pages = 943–956 | date = January 2014 | pmid = 24574767 | pmc = 3921546 | doi = 10.3748/wjg.v20.i4.943 | doi-access = free }}</ref>

===Genomics and epigenomics===

Consensus molecular subtypes (CMS) classification of colorectal cancer was first introduced in 2015. CMS classification so far has been considered the most robust classification system available for CRC that has a clear biological interpretability and the basis for future clinical stratification and subtype-based targeted interventions.<ref>{{cite journal | vauthors = Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E, Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S | title = The consensus molecular subtypes of colorectal cancer | journal = Nature Medicine | volume = 21 | issue = 11 | pages = 1350–1356 | date = November 2015 | pmid = 26457759 | pmc = 4636487 | doi = 10.1038/nm.3967 }}</ref>

A novel Epigenome-based Classification (EpiC) of colorectal cancer was proposed in 2021 introducing 4 enhancer subtypes in people with CRC. Chromatin states using 6 histone marks are characterized to identify EpiC subtypes. A combinatorial therapeutic approach based on the previously introduced consensus molecular subtypes (CMSs) and EpiCs could significantly enhance current treatment strategies.<ref>{{cite journal | vauthors = Orouji E, Raman AT, Singh AK, Sorokin A, Arslan E, Ghosh AK, Schulz J, Terranova C, Jiang S, Tang M, Maitituoheti M, Callahan SC, Barrodia P, Tomczak K, Jiang Y, Jiang Z, Davis JS, Ghosh S, Lee HM, Reyes-Uribe L, Chang K, Liu Y, Chen H, Azhdarinia A, Morris J, Vilar E, Carmon KS, Kopetz SE, Rai K | title = Chromatin state dynamics confers specific therapeutic strategies in enhancer subtypes of colorectal cancer | journal = Gut | date = May 2021 | volume = 71 | issue = 5 | pages = 938–949 | pmid = 34059508 | doi = 10.1136/gutjnl-2020-322835 | pmc = 8745382 | s2cid = 235269540 }}</ref>

==Diagnosis==
[[File:ColonCaWithMetsMark.png|thumb|Colon cancer with extensive metastases to the liver]]
Colorectal cancer diagnosis is performed by sampling of areas of the colon suspicious for possible tumor development, typically during colonoscopy or sigmoidoscopy, depending on the location of the lesion.<ref name=Lancet10/>

===Medical imaging===
A colorectal cancer is sometimes initially discovered on [[CT scan]].<ref name="Colorectal Cancer">{{cite web |url=https://www.lecturio.com/concepts/colorectal-cancer/| title=Colorectal Cancer|website=The Lecturio Medical Concept Library |access-date= 10 July 2021}}</ref>

Presence of [[Metastasis|metastases]] is determined by a [[X-ray computed tomography|CT scan]] of the chest, abdomen and pelvis.<ref name="Lancet10"/> Other potential imaging tests such as [[Positron emission tomography|PET]] and [[MRI]] may be used in certain cases.<ref name="Lancet10" /> MRI is particularly useful to determine local stage of the tumor and to plan the optimal surgical approach.<ref name="Colorectal Cancer"/>

MRI is also performed after completion of neoadjuvant chemoradiotherapy to identify patients who achieve complete response. Patients with complete response on both MRI and endoscopy may not require surgical resection and can avoid unnecessary surgical morbidity and complications.<ref>{{cite journal |last1=Awiwi |first1=MO |last2=Kaur |first2=H |last3=Ernst |first3=R |last4=Rauch |first4=GM |last5=Morani |first5=AC |last6=Stanietzky |first6=N |last7=Palmquist |first7=SM |last8=Salem |first8=UI |title=Restaging MRI of Rectal Adenocarcinoma after Neoadjuvant Chemoradiotherapy: Imaging Findings and Potential Pitfalls. |journal=Radiographics |year=2023 |volume=43 |issue=4 |pages=e220135 |doi=10.1148/rg.220135 |pmid=36927125|s2cid=257583845 }}</ref> Patients selected for non-surgical treatment of rectal cancer should have periodic MRI scans, receive physical examinations, and undergo endoscopy procedures to detect any tumor re-growth which can occur in a minority of these patients. When local recurrence occurs, periodic follow up can detect it when it is still small and curable with salvage surgery. In addition, MRI tumor regression grades can be assigned after chemoradiotherapy which correlate with patients' long-term survival outcomes.<ref>{{cite journal |last1=Awiwi |first1=MO |last2=Kaur |first2=H |last3=Ernst |first3=R |last4=Rauch |first4=GM |last5=Morani |first5=AC |last6=Stanietzky |first6=N |last7=Palmquist |first7=SM |last8=Salem |first8=UI |title=Restaging MRI of Rectal Adenocarcinoma after Neoadjuvant Chemoradiotherapy: Imaging Findings and Potential Pitfalls. |journal=Radiographics |date=April 2023 |volume=43 |issue=4 |pages=e220135 |doi=10.1148/rg.220135 |pmid=36927125|s2cid=257583845 }}</ref>

===Histopathology===
[[File:Relative incidence of colorectal cancers.svg|thumb|Relative incidence of various histopathological types of colorectal cancer. The vast majority of colorectal cancers are [[adenocarcinoma]]s.<ref>{{cite journal | vauthors = Kang H, O'Connell JB, Leonardi MJ, Maggard MA, McGory ML, Ko CY | title = Rare tumors of the colon and rectum: a national review | journal = International Journal of Colorectal Disease | volume = 22 | issue = 2 | pages = 183–189 | date = February 2007 | pmid = 16845516 | doi = 10.1007/s00384-006-0145-2 | s2cid = 34693873 }}</ref>]]
[[File:Micrograph of colorectal carcinoma with dirty necrosis.jpg|thumb|Micrograph of colorectal adenocarcinoma, showing "dirty necrosis".]]
{{Further|Histopathology of colorectal adenocarcinoma}}
The [[histopathology|histopathologic]] characteristics of the [[tumor]] are reported from the analysis of tissue taken from a biopsy or surgery. A pathology report contains a description of the microscopical characteristics of the tumor tissue, including both tumor cells and how the tumor invades into healthy tissues and finally if the tumor appears to be completely removed. The most common form of colon cancer is [[adenocarcinoma]], constituting between 95%<ref>{{cite web|url=https://seer.cancer.gov/tools/solidtumor/Colon_STM.pdf|title=Colon, Rectosigmoid, and Rectum Equivalent Terms and Definitions C180-C189, C199, C209, (Excludes lymphoma and leukemia M9590 – M9992 and Kaposi sarcoma M9140) – Colon Solid Tumor Rules 2018. July 2019 Update|website=[[National Cancer Institute]]|archive-url=https://web.archive.org/web/20200116094025/https://seer.cancer.gov/tools/solidtumor/Colon_STM.pdf|archive-date=January 16, 2020|url-status=live}}</ref> and 98%<ref>{{cite web|url=https://www.cancercenter.com/cancer-types/colorectal-cancer/types|title=Colorectal cancer types|website=[[Cancer Treatment Centers of America]]|date=October 4, 2018|access-date=2020-01-16}}</ref> of all cases of colorectal cancer. Other, rarer types include [[lymphoma]], adenosquamous and [[squamous cell carcinoma]]. Some subtypes are more aggressive.<ref>{{cite journal| vauthors = Di Como JA, Mahendraraj K, Lau CS, Chamberlain RS |title=Adenosquamous carcinoma of the colon and rectum: a population based clinical outcomes study involving 578 patients from the Surveillance Epidemiology and End Result (SEER) database (1973–2010)|journal=Journal of the American College of Surgeons|date=October 2015|volume=221|issue=4|page=56|doi=10.1016/j.jamcollsurg.2015.08.044}}</ref> [[Immunohistochemistry]] may be used in uncertain cases.<ref>{{cite journal | vauthors = Whiteside G, Munglani R | title = TUNEL, Hoechst and immunohistochemistry triple-labelling: an improved method for detection of apoptosis in tissue sections--an update | journal = Brain Research. Brain Research Protocols | volume = 3 | issue = 1 | pages = 52–53 | date = September 1998 | pmid = 9767106 | doi = 10.1016/s1385-299x(98)00020-8 }}
</ref>

===Staging===
{{Main|Colon cancer staging}}
[[Cancer staging|Staging]] of the cancer is based on both radiological and pathological findings. As with most other forms of cancer, tumor staging is based on the [[TNM staging system|TNM system]] which considers how much the initial tumor has spread and the presence of metastases in lymph nodes and more distant organs.<ref name="Lancet10" /> The AJCC 8th edition was published in 2018.<ref>{{Cite web|url=http://www.pathologyoutlines.com/topic/colontumorstaging8ed.html|title=TNM staging of colorectal carcinoma (AJCC 8th edition)|website=www.pathologyoutlines.com|access-date=2019-02-24}}</ref>

==Prevention==
It has been estimated that about half of colorectal cancer cases are due to lifestyle factors, and about a quarter of all cases are preventable.<ref>{{cite journal | vauthors = Parkin DM, Boyd L, Walker LC | title = 16. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010 | journal = British Journal of Cancer | volume = 105 | issue = S2 | pages = S77–S81 | date = December 2011 | pmid = 22158327 | pmc = 3252065 | doi = 10.1038/bjc.2011.489 | df = mdy-all }}</ref> Increasing surveillance, engaging in physical activity, consuming a diet high in fiber, quitting smoking and limiting alcohol consumption decrease the risk.<ref>{{cite book|url=https://books.google.com/books?id=qfN8Y1_lbDYC&pg=PA809|title=Cancer Epidemiology and Prevention| vauthors = Searke D |publisher=Oxford University Press|year=2006|isbn=978-0-19-974797-9|edition=3|page=809|url-status=live|archive-url=https://web.archive.org/web/20150928202401/https://books.google.com/books?id=qfN8Y1_lbDYC&pg=PA809|archive-date=September 28, 2015|df=mdy-all}}</ref><ref>{{cite book|url=https://books.google.com/books?id=FTQ_AAAAQBAJ&pg=PA179|title=Cancer Prevention| vauthors = Rennert G |publisher=Springer|year=2007|isbn=978-3-540-37696-5|page=179|url-status=live|archive-url=https://web.archive.org/web/20151003213802/https://books.google.com/books?id=FTQ_AAAAQBAJ&pg=PA179|archive-date=October 3, 2015|df=mdy-all}}</ref>

===Lifestyle===
Lifestyle risk factors with strong evidence include lack of exercise, cigarette smoking, alcohol, and obesity.<ref name="NCI2018Overview">{{cite web |title=Colorectal Cancer Prevention Overview |url=https://www.cancer.gov/types/colorectal/hp/colorectal-prevention-pdq#link/_150_toc |website=National Cancer Institute |access-date=26 October 2018 |language=en |date=1 March 2018}}</ref><ref name="WHOcancerprevention">{{cite web |title=Cancer prevention |url=https://www.who.int/cancer/prevention/en/ |publisher=World Health Organization |access-date=27 October 2018}}</ref><ref>{{cite journal | vauthors = Chaplin A, Rodriguez RM, Segura-Sampedro JJ, Ochogavía-Seguí A, Romaguera D, Barceló-Coblijn G | title = Insights behind the Relationship between Colorectal Cancer and Obesity: Is Visceral Adipose Tissue the Missing Link? | journal = International Journal of Molecular Sciences | volume = 23 | issue = 21 | pages = 13128 | date = October 2022 | pmid = 36361914 | pmc = 9655590 | doi = 10.3390/ijms232113128 | doi-access = free }}</ref> The risk of colon cancer can be reduced by maintaining a normal body weight through a combination of sufficient exercise and eating a [[healthy diet]].<ref>{{cite journal | vauthors = Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K | title = Body Fatness and Cancer--Viewpoint of the IARC Working Group | journal = The New England Journal of Medicine | volume = 375 | issue = 8 | pages = 794–798 | date = August 2016 | pmid = 27557308 | pmc = 6754861 | doi = 10.1056/nejmsr1606602 }}</ref>

<!-- Diet -->
Current research consistently links eating more red meat and processed meat to a higher risk of the disease.<ref>{{Cite web|url=https://www.cancer.net/cancer-types/colorectal-cancer/risk-factors-and-prevention|title=Colorectal Cancer – Risk Factors and Prevention|date=June 25, 2012}}</ref> Starting in the 1970s, dietary recommendations to prevent colorectal cancer often included increasing the consumption of [[whole grain]]s, fruits and vegetables, and reducing the intake of [[red meat]] and [[processed meat]]s. This was based on animal studies and retrospective observational studies. However, large scale prospective studies have failed to demonstrate a significant protective effect, and due to the multiple causes of cancer and the complexity of studying correlations between diet and health, it is uncertain whether any specific dietary interventions will have significant protective effects.<ref name="WCR2014Willett">{{cite book | vauthors = Willett WC | veditors = Stewart BW, Wild CP |title=World Cancer Report |date=2014 |publisher=the International Agency for Research on Cancer, World Health Organization |isbn=978-92-832-0443-5 |pages=432–435 |chapter-url=http://publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014 |chapter=Diet, nutrition, and cancer: where next for public health?}}</ref>{{rp|432–433}}<ref name=WCR2014_2.6/>{{rp|125–126}} In 2018 the [[National Cancer Institute]] stated that "There is no reliable evidence that a diet started in adulthood that is low in fat and meat and high in fiber, fruits, and vegetables reduces the risk of CRC by a clinically important degree."<ref name=NCI2018Overview/><ref name="NCI2018Evidence">{{cite web |title=Colorectal Cancer Prevention Description of Evidence |url=https://www.cancer.gov/types/colorectal/hp/colorectal-prevention-pdq#section/_29 |website=National Cancer Institute |access-date=26 October 2018 |language=en |date=1 March 2018}}</ref>

Consuming alcoholic drinks and consuming processed meat both increase the risk of colorectal cancer.<ref name="w151">{{cite journal | last1=Tuan | first1=Juan | last2=Chen | first2=Ying-Xuan | title=Dietary and Lifestyle Factors Associated with Colorectal Cancer Risk and Interactions with Microbiota: Fiber, Red or Processed Meat and Alcoholic Drinks | journal=Gastrointestinal Tumors | publisher=S. Karger AG | volume=3 | issue=1 | date=2015-12-18 | issn=2296-3774 | doi=10.1159/000442831 | pages=17–24| pmid=27722153 | pmc=5040877 }}</ref>

The 2014 World Health Organization cancer report noted that it has been hypothesized that dietary fiber might help prevent colorectal cancer, but that most studies at the time had not yet studied the correlation.<ref name="WCR2014_2.6">{{cite book | vauthors = Willett WC, Key T, Romieu I | veditors = Stewart BW, Wild CP |title=World Cancer Report |date=2014 |publisher=the International Agency for Research on Cancer, World Health Organization |isbn=978-92-832-0443-5 |pages=124–133 |chapter-url=http://publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014 |chapter=Chapter 2.6: Diet, obesity, and physical activity|quote=Several large prospective cohort studies of dietary fibre and colon cancer risk have not supported an association, although an inverse relation was seen in the large European Prospective Investigation into Cancer and Nutrition (EPIC) study and a recent meta-analysis. The variation in findings from prospective studies needs to be better understood; dietary fibre is complex and heterogeneous, and the relation with colorectal cancer could differ by dietary source. (p. 127)}}</ref> A 2019 review, however, found evidence of benefit from dietary fiber and whole grains.<ref>{{cite journal | vauthors = Reynolds A, Mann J, Cummings J, Winter N, Mete E, Te Morenga L | title = Carbohydrate quality and human health: a series of systematic reviews and meta-analyses | journal = Lancet | volume = 393 | issue = 10170 | pages = 434–445 | date = February 2019 | pmid = 30638909 | doi = 10.1016/S0140-6736(18)31809-9 | s2cid = 58632705 | doi-access = free }}</ref> The [[World Cancer Research Fund]] listed the benefit of fiber for prevention of colorectal cancer as "probable" as of 2017.<ref name="Song2018">{{cite journal | vauthors = Song M, Chan AT | title = Environmental Factors, Gut Microbiota, and Colorectal Cancer Prevention | journal = Clinical Gastroenterology and Hepatology | volume = 17 | issue = 2 | pages = 275–289 | date = January 2019 | pmid = 30031175 | pmc = 6314893 | doi = 10.1016/j.cgh.2018.07.012 | quote = Despite the longstanding hypothesis that a high-fiber diet may protect against colorectal cancer... epidemiologic studies associating dietary fiber intake with subsequent risk of colorectal cancer have yielded inconsistent results... Nonetheless, based on existing evidence, the most recent expert report from the World Cancer Research Fund and American Institute for Cancer Research in 2017 concludes that there is probable evidence }}</ref> A 2022 [[umbrella review]] says there is "convincing evidence" for that association.<ref>{{cite journal | vauthors = Jabbari M, Pourmoradian S, Eini-Zinab H, Mosharkesh E, Hosseini Balam F, Yaghmaei Y, Yadegari A, Amini B, Arman Moghadam D, Barati M, Hekmatdoost A | title = Levels of evidence for the association between different food groups/items consumption and the risk of various cancer sites: an umbrella review | journal = International Journal of Food Sciences and Nutrition | volume = 73 | issue = 7 | pages = 861–874 | date = November 2022 | pmid = 35920747 | doi = 10.1080/09637486.2022.2103523 | s2cid = 251280745 }}</ref>

<!-- Exercise -->
Higher physical activity is recommended.<ref name=WCRF2011/><ref>{{cite journal | vauthors = Pérez-Cueto FJ, Verbeke W | title = Consumer implications of the WCRF's permanent update on colorectal cancer | journal = Meat Science | volume = 90 | issue = 4 | pages = 977–978 | date = April 2012 | pmid = 22196090 | doi = 10.1016/j.meatsci.2011.11.032 }}</ref> [[Physical exercise]] is associated with a modest reduction in colon but not rectal cancer risk.<ref name="pmid19207713">{{cite journal | vauthors = Harriss DJ, Atkinson G, Batterham A, George K, Cable NT, Reilly T, Haboubi N, Renehan AG | title = Lifestyle factors and colorectal cancer risk (2): a systematic review and meta-analysis of associations with leisure-time physical activity | journal = Colorectal Disease | volume = 11 | issue = 7 | pages = 689–701 | date = September 2009 | pmid = 19207713 | doi = 10.1111/j.1463-1318.2009.01767.x | s2cid = 8026021 }}</ref><ref>{{cite journal | vauthors = Robsahm TE, Aagnes B, Hjartåker A, Langseth H, Bray FI, Larsen IK | title = Body mass index, physical activity, and colorectal cancer by anatomical subsites: a systematic review and meta-analysis of cohort studies | journal = European Journal of Cancer Prevention | volume = 22 | issue = 6 | pages = 492–505 | date = November 2013 | pmid = 23591454 | doi = 10.1097/CEJ.0b013e328360f434 | s2cid = 24764995 }}</ref> High levels of physical activity reduce the risk of colon cancer by about 21%.<ref name="BMJ2016">{{cite journal | vauthors = Kyu HH, Bachman VF, Alexander LT, Mumford JE, Afshin A, Estep K, Veerman JL, Delwiche K, Iannarone ML, Moyer ML, Cercy K, Vos T, Murray CJ, Forouzanfar MH | title = Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013 | journal = BMJ | volume = 354 | pages = i3857 | date = August 2016 | pmid = 27510511 | pmc = 4979358 | doi = 10.1136/bmj.i3857 }}</ref> [[Sitting]] regularly for prolonged periods is associated with higher mortality from colon cancer. Regular exercise does not negate the risk but does lower it.<ref name="Biswas">{{cite journal | vauthors = Biswas A, Oh PI, Faulkner GE, Bajaj RR, Silver MA, Mitchell MS, Alter DA | title = Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis | journal = Annals of Internal Medicine | volume = 162 | issue = 2 | pages = 123–132 | date = January 2015 | pmid = 25599350 | doi = 10.7326/M14-1651 | s2cid = 7256176 }}</ref>

===Medication and supplements===
[[Aspirin]] and [[celecoxib]] appear to decrease the risk of colorectal cancer in those at high risk.<ref name="pmid20594533">{{cite journal | vauthors = Cooper K, Squires H, Carroll C, Papaioannou D, Booth A, Logan RF, Maguire C, Hind D, Tappenden P | title = Chemoprevention of colorectal cancer: systematic review and economic evaluation | journal = Health Technology Assessment | volume = 14 | issue = 32 | pages = 1–206 | date = June 2010 | pmid = 20594533 | doi = 10.3310/hta14320 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Emilsson L, Holme Ø, Bretthauer M, Cook NR, Buring JE, Løberg M, Adami HO, Sesso HD, Gaziano MJ, Kalager M | title = Systematic review with meta-analysis: the comparative effectiveness of aspirin vs. screening for colorectal cancer prevention | journal = Alimentary Pharmacology & Therapeutics | volume = 45 | issue = 2 | pages = 193–204 | date = January 2017 | pmid = 27859394 | doi = 10.1111/apt.13857 | doi-access = free }}</ref> Aspirin is recommended in those who are 50 to 60 years old, do not have an increased risk of bleeding, and are at risk for cardiovascular disease to prevent colorectal cancer.<ref>{{cite journal | vauthors = Bibbins-Domingo K | title = Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement | journal = Annals of Internal Medicine | volume = 164 | issue = 12 | pages = 836–845 | date = June 2016 | pmid = 27064677 | doi = 10.7326/M16-0577 | doi-access = free }}</ref> It is not recommended in those at average risk.<ref>{{cite web |title=Aspirin or Nonsteroidal Anti-inflammatory Drugs for the Primary Prevention of Colorectal Cancer |url=http://www.ahrq.gov/clinic/pocketgd1011/gcp10s2.htm |author=Agency for Healthcare Research and Quality |quote=2010/2011 |publisher=United States Department of Health & Human Services |url-status=live |archive-url=https://web.archive.org/web/20160105033942/http://www.ahrq.gov/clinic/pocketgd1011/gcp10s2.htm |archive-date=January 5, 2016 |df=mdy-all }}</ref>

There is tentative evidence for [[calcium]] supplementation, but it is not sufficient to make a recommendation.<ref name="pmid18254022">{{cite journal | vauthors = Weingarten MA, Zalmanovici A, Yaphe J | title = Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD003548 | date = January 2008 | volume = 2010 | pmid = 18254022 | doi = 10.1002/14651858.CD003548.pub4 | pmc = 8719254 }}</ref>

Adequate [[Vitamin D]] intake and blood levels are associated with a lower risk of colon cancer.<ref name="pmid21876081">{{cite journal | vauthors = Ma Y, Zhang P, Wang F, Yang J, Liu Z, Qin H | title = Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies | journal = Journal of Clinical Oncology | volume = 29 | issue = 28 | pages = 3775–3782 | date = October 2011 | pmid = 21876081 | doi = 10.1200/JCO.2011.35.7566 | doi-access = free }}</ref><ref name="pmid21672549">{{cite journal | vauthors = Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H | title = Meta-analysis: Serum vitamin D and colorectal adenoma risk | journal = Preventive Medicine | volume = 53 | issue = 1–2 | pages = 10–16 | date = 2011 | pmid = 21672549 | doi = 10.1016/j.ypmed.2011.05.013 }}</ref>

===Screening===
As more than 80% of colorectal cancers arise from [[adenomatous polyps]], screening for this cancer is effective for both early detection and for prevention.<ref name=Lancet10/><ref name="cdcprevent">{{cite web |title=What Can I Do to Reduce My Risk of Colorectal Cancer? |url=https://www.cdc.gov/cancer/colorectal/basic_info/prevention.htm |website=Centers for Disease Control and Prevention |date=April 2, 2014 |access-date=March 5, 2015 |url-status=live |archive-url=https://web.archive.org/web/20150226154956/http://www.cdc.gov/cancer/colorectal/basic_info/prevention.htm |archive-date=February 26, 2015 |df=mdy-all }}</ref> Diagnosis of cases of colorectal cancer through screening tends to occur 2–3 years before diagnosis of cases with symptoms.<ref name=Lancet10/> Any polyps that are detected can be removed, usually by [[colonoscopy]] or [[sigmoidoscopy]], and thus prevent them from turning into cancer. Screening has the potential to reduce colorectal cancer deaths by 60%.<ref name=Screen11/>

The three main screening tests are colonoscopy, [[fecal occult blood]] testing, and [[flexible sigmoidoscopy]]. Of the three, only sigmoidoscopy cannot screen the [[Colon (anatomy)#Right and Left Colon|right side of the colon]] where 42% of cancers are found.<ref name="Siegel2012Intro">{{cite journal | vauthors = Siegel RL, Ward EM, Jemal A | title = Trends in colorectal cancer incidence rates in the United States by tumor location and stage, 1992-2008 | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 21 | issue = 3 | pages = 411–416 | date = March 2012 | pmid = 22219318 | doi = 10.1158/1055-9965.EPI-11-1020 | doi-access = free }}</ref> Flexible sigmoidoscopy, however, has the best evidence for decreasing the risk of death from any cause.<ref>{{cite journal | vauthors = Swartz AW, Eberth JM, Josey MJ, Strayer SM | title = Reanalysis of All-Cause Mortality in the U.S. Preventive Services Task Force 2016 Evidence Report on Colorectal Cancer Screening | journal = Annals of Internal Medicine | volume = 167 | issue = 8 | pages = 602–603 | date = October 2017 | pmid = 28828493 | pmc = 5823607 | doi = 10.7326/M17-0859 }}</ref>

Fecal occult blood testing (FOBT) of the stool is typically recommended every two years and can be either [[Stool guaiac test|guaiac-based]] or [[Immunochemistry|immunochemical]].<ref name=Lancet10/> If abnormal FOBT results are found, participants are typically referred for a follow-up colonoscopy examination. When done once every 1–2 years, FOBT screening reduces colorectal cancer deaths by 16% and among those participating in screening, colorectal cancer deaths can be reduced up to 23%, although it has not been proven to reduce all-cause mortality.<ref>{{cite journal | vauthors = Hewitson P, Glasziou P, Watson E, Towler B, Irwig L | title = Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (hemoccult): an update | journal = The American Journal of Gastroenterology | volume = 103 | issue = 6 | pages = 1541–1549 | date = June 2008 | doi = 10.1111/j.1572-0241.2008.01875.x | pmid = 18479499 | s2cid = 26338156 }}</ref> Immunochemical tests are accurate and do not require dietary or medication changes before testing.<ref>{{cite journal | vauthors = Lee JK, Liles EG, Bent S, Levin TR, Corley DA | title = Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis | journal = Annals of Internal Medicine | volume = 160 | issue = 3 | pages = 171 | date = February 2014 | pmid = 24658694 | pmc = 4189821 | doi = 10.7326/M13-1484 }}</ref> However, research in the UK has found that for these immunochemical tests, the threshold for further investigation is set at a point that may miss more than half of bowel cancer cases. The research suggests that the [[NHS England|NHS England's]] Bowel Cancer Screening Programme could make better use of the test's ability to provide the exact concentration of blood in faeces (rather than only whether it is above or below a cutoff level).<ref>{{Cite journal |date=2021-09-13 |title=New pathways could improve bowel cancer screening |url=https://evidence.nihr.ac.uk/alert/new-pathways-could-improve-bowel-screening-programme/ |access-date=2022-08-05 |website=NIHR Evidence |doi=10.3310/alert_47581 |s2cid=239113610 |language=en-GB}}</ref><ref name="Li-2021">{{cite journal | vauthors = Li SJ, Sharples LD, Benton SC, Blyuss O, Mathews C, Sasieni P, Duffy SW | title = Faecal immunochemical testing in bowel cancer screening: Estimating outcomes for different diagnostic policies | journal = Journal of Medical Screening | volume = 28 | issue = 3 | pages = 277–285 | date = September 2021 | pmid = 33342370 | pmc = 8366184 | doi = 10.1177/0969141320980501 }}</ref>

Other options include [[virtual colonoscopy]] and stool DNA screening testing (FIT-DNA). Virtual colonoscopy via a [[CT scan]] appears as good as standard colonoscopy for detecting cancers and large adenomas but is expensive, associated with radiation exposure, and cannot remove any detected abnormal growths as standard colonoscopy can.<ref name=Lancet10/> Stool DNA screening test looks for [[biomarker]]s associated with colorectal cancer and precancerous lesions, including altered [[DNA]] and [[Hemoglobin A|blood hemoglobin]]. A positive result should be followed by [[colonoscopy]]. FIT-DNA has more false positives than FIT and thus results in more adverse effects.<ref name=USPSTF2016/> Further study is required as of 2016 to determine whether a three-year screening interval is correct.<ref name="USPSTF2016"/>

====Recommendations====
In the United States, screening is typically recommended between ages 50 and 75&nbsp;years.<ref name=USPSTF2016/><ref name=Qa2019>{{cite journal | vauthors = Qaseem A, Crandall CJ, Mustafa RA, Hicks LA, Wilt TJ, Forciea MA, Fitterman N, Horwitch CA, Kansagara D, Maroto M, McLean RM, Roa J, Tufte J | title = Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults: A Guidance Statement From the American College of Physicians | journal = Annals of Internal Medicine | volume = 171 | issue = 9 | pages = 643–654 | date = November 2019 | pmid = 31683290 | pmc = 8152103 | doi = 10.7326/M19-0642 | doi-access = free }}</ref> The [[American Cancer Society]] recommends starting at the age of 45.<ref>{{cite journal | vauthors = Wolf AM, Fontham ET, Church TR, Flowers CR, Guerra CE, LaMonte SJ, Etzioni R, McKenna MT, Oeffinger KC, Shih YT, Walter LC, Andrews KS, Brawley OW, Brooks D, Fedewa SA, Manassaram-Baptiste D, Siegel RL, Wender RC, Smith RA | title = Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society | journal = CA: A Cancer Journal for Clinicians | volume = 68 | issue = 4 | pages = 250–281 | date = July 2018 | pmid = 29846947 | doi = 10.3322/caac.21457 | doi-access = free }}</ref> For those between 76 and 85 years old, the decision to screen should be individualized.<ref name=USPSTF2016/> For those at high risk, screenings usually begin at around 40.<ref name=Lancet10/><ref name="USPTF2008">{{cite web|url=http://www.uspreventiveservicestaskforce.org/uspstf/uspscolo.htm|title=Screening for Colorectal Cancer|year=2008|work=[[U.S. Preventive Services Task Force]]|url-status=dead|archive-url=https://web.archive.org/web/20150207110937/http://www.uspreventiveservicestaskforce.org/uspstf/uspscolo.htm|archive-date=February 7, 2015|df=mdy-all|access-date=December 19, 2011}}</ref>

Several screening methods are recommended including stool-based tests every 2 years, [[sigmoidoscopy]] every 10 years with [[fecal immunochemical testing]] every two years, and [[colonoscopy]] every 10 years.<ref name=Qa2019/> It is unclear which of these two methods is better.<ref name=Bren2014/> Colonoscopy may find more cancers in the first part of the colon, but is associated with greater cost and more complications.<ref name="Bren2014">{{cite journal | vauthors = Brenner H, Stock C, Hoffmeister M | title = Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of randomised controlled trials and observational studies | journal = BMJ | volume = 348 | issue = apr09 1 | pages = g2467 | date = April 2014 | pmid = 24922745 | pmc = 3980789 | doi = 10.1136/bmj.g2467 }}</ref> For people with average risk who have had a high-quality colonoscopy with normal results, the [[American Gastroenterological Association]] does not recommend any type of screening in the 10 years following the colonoscopy.<ref name="AGAfive">{{Cite journal|publisher=[[American Gastroenterological Association]] |title=Five Things Physicians and Patients Should Question |journal=Choosing Wisely: An Initiative of the ABIM Foundation |url=http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_AGA.pdf |access-date=August 17, 2012 |url-status=dead |archive-url=https://web.archive.org/web/20120809143636/http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_AGA.pdf |archive-date=August 9, 2012 |df=mdy }}</ref><ref name="coloscreen">{{cite journal | vauthors = Winawer S, Fletcher R, Rex D, Bond J, Burt R, Ferrucci J, Ganiats T, Levin T, Woolf S, Johnson D, Kirk L, Litin S, Simmang C | title = Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence | journal = Gastroenterology | volume = 124 | issue = 2 | pages = 544–560 | date = February 2003 | pmid = 12557158 | doi = 10.1053/gast.2003.50044 | s2cid = 29354772 | doi-access = free }}</ref> For people over 75 or those with a life expectancy of less than 10&nbsp;years, screening is not recommended.<ref>{{cite journal | vauthors = Qaseem A, Denberg TD, Hopkins RH, Humphrey LL, Levine J, Sweet DE, Shekelle P | title = Screening for colorectal cancer: a guidance statement from the American College of Physicians | journal = Annals of Internal Medicine | volume = 156 | issue = 5 | pages = 378–386 | date = March 2012 | pmid = 22393133 | doi = 10.7326/0003-4819-156-5-201203060-00010 | df = mdy-all | doi-access = free }}</ref> It takes about 10 years after screening for one out of a 1000 people to benefit.<ref>{{cite journal | vauthors = Tang V, Boscardin WJ, Stijacic-Cenzer I, Lee SJ | title = Time to benefit for colorectal cancer screening: survival meta-analysis of flexible sigmoidoscopy trials | journal = BMJ | volume = 350 | pages = h1662 | date = April 2015 | pmid = 25881903 | pmc = 4399600 | doi = 10.1136/bmj.h1662 }}</ref> The USPSTF list seven potential strategies for screening, with the most important thing being that at least one of these strategies is appropriately used.<ref name=USPSTF2016/>

In Canada, among those 50 to 75 years old at normal risk, fecal immunochemical testing or FOBT is recommended every two years or sigmoidoscopy every 10 years.<ref name=CMAJ2016/> Colonoscopy is less preferred.<ref name="CMAJ2016">{{cite journal | vauthors = Bacchus CM, Dunfield L, Gorber SC, Holmes NM, Birtwhistle R, Dickinson JA, Lewin G, Singh H, Klarenbach S, Mai V, Tonelli M | title = Recommendations on screening for colorectal cancer in primary care | journal = CMAJ | volume = 188 | issue = 5 | pages = 340–348 | date = March 2016 | pmid = 26903355 | pmc = 4786388 | doi = 10.1503/cmaj.151125 }}</ref>

Some countries have national colorectal screening programs which offer FOBT screening for all adults within a certain age group, typically starting between ages 50 and 60. Examples of countries with organised screening include the United Kingdom,<ref>{{cite web|url=http://www.cancerscreening.nhs.uk/bowel/|title=NHS Bowel Cancer Screening Programme|work=cancerscreening.nhs.uk|url-status=live|archive-url=https://web.archive.org/web/20141129023758/http://www.cancerscreening.nhs.uk/bowel/|archive-date=November 29, 2014|df=mdy-all}}</ref> Australia,<ref>{{cite web|url=https://www.bowelcanceraustralia.org/bca/ |title=Home – Bowel Cancer Australia |work=bowelcanceraustralia.org |url-status=dead |archive-url=https://web.archive.org/web/20141224130423/https://www.bowelcanceraustralia.org/bca/ |archive-date=December 24, 2014 |df=mdy }}</ref> the Netherlands,<ref>{{cite web|url=http://www.rivm.nl/Onderwerpen/B/Bevolkingsonderzoek_darmkanker|title=Bevolkingsonderzoek darmkanker|work=rivm.nl|url-status=live|archive-url=https://web.archive.org/web/20141217020915/http://www.rivm.nl/Onderwerpen/B/Bevolkingsonderzoek_darmkanker/|archive-date=December 17, 2014|df=mdy-all}}</ref> Hong Kong, and Taiwan.<ref>{{cite journal | vauthors = Tepus M, Yau TO | title = Non-Invasive Colorectal Cancer Screening: An Overview | journal = Gastrointestinal Tumors | volume = 7 | issue = 3 | pages = 62–73 | date = July 2020 | pmid = 32903904 | pmc = 7445682 | doi = 10.1159/000507701 | doi-access = free }}</ref>

The UK Bowel Cancer Screening Programme aims to find warning signs in people aged 60 to 74, by recommending a faecal immunochemical test (FIT) every two years. FIT measures blood in faeces, and people with levels above a certain threshold may have bowel tissue examined for signs of cancer. Growths having cancerous potential are removed.<ref>{{Cite journal|url=https://evidence.nihr.ac.uk/alert/new-pathways-could-improve-bowel-screening-programme/|title=New pathways could improve bowel cancer screening|date=September 13, 2021|website=NIHR Evidence|doi=10.3310/alert_47581 |s2cid=239113610 }}</ref><ref name="Li-2021"/>

==Treatment==
The treatment of colorectal cancer can be aimed at cure or palliation. The decision on which aim to adopt depends on various factors, including the person's health and preferences, as well as the stage of the tumor.<ref name="pmid21943995">{{cite journal | vauthors = Stein A, Atanackovic D, Bokemeyer C | title = Current standards and new trends in the primary treatment of colorectal cancer | journal = European Journal of Cancer | volume = 47 | issue = Suppl 3 | pages = S312–S314 | date = September 2011 | pmid = 21943995 | doi = 10.1016/S0959-8049(11)70183-6 }}</ref> Assessment in multidisciplinary teams is a critical part of determining whether the patient is suitable for surgery or not.<ref>{{cite journal | vauthors = Chiorean EG, Nandakumar G, Fadelu T, Temin S, Alarcon-Rozas AE, Bejarano S, Croitoru AE, Grover S, Lohar PV, Odhiambo A, Park SH, Garcia ER, Teh C, Rose A, Zaki B, Chamberlin MD | title = Treatment of Patients With Late-Stage Colorectal Cancer: ASCO Resource-Stratified Guideline | journal = JCO Global Oncology | volume = 6 | issue = 6 | pages = 414–438 | date = March 2020 | pmid = 32150483 | pmc = 7124947 | doi = 10.1200/JGO.19.00367 }}</ref> When colorectal cancer is caught early, surgery can be curative.<!--<ref name=Lancet10/>--> However, when it is detected at later stages (for which [[metastasis|metastases]] are present), this is less likely and treatment is often directed at palliation, to relieve symptoms caused by the tumour and keep the person as comfortable as possible.<ref name="Lancet10" />

===Surgery===
[[File:Diagram showing a local resection of an early stage bowel cancer CRUK 068.svg|thumb|A diagram of a local resection of early stage colon cancer]]
[[File:Diagram showing the area removed for a rectal cancer CRUK 286.svg|thumb|A diagram of local surgery for rectal cancer]]
[[File:Edges and margins in intestinal tumor.png|thumb|Margins of a colonic resection.]]
At an early stage, colorectal cancer may be removed during a colonoscopy using one of several techniques, including [[endoscopic mucosal resection]] or [[endoscopic submucosal dissection]].<ref name=NCI2014PtTx/> Endoscopic resection is possible if there is low possibility of lymph node metastasis and the size and location of the tumor make en bloc resection possible.<ref>{{Cite journal|last1=Yamashita |first1=Ken |last2=Oka |first2=Shiro |last3=Tanaka |first3=Shinji |last4=Nagata |first4=Shinji |last5=Kuwai |first5=Toshio |last6=Furudoi |first6=Akira |last7=Tamura |first7=Tadamasa |last8=Kunihiro |first8=Masaki |last9=Okanobu |first9=Hideharu |last10=Nakadoi |first10=Koichi |last11=Kanao |first11=Hiroyuki |last12=Higashiyama |first12=Makoto |last13=Arihiro |first13=Koji |last14=Kuraoka |first14=Kazuya |last15=Shimamoto |first15=Fumio |date=2019-03-01 |title=Long-term prognosis after treatment for T1 carcinoma of laterally spreading tumors: a multicenter retrospective study |url=https://doi.org/10.1007/s00384-018-3203-7 |journal=International Journal of Colorectal Disease |language=en |volume=34 |issue=3 |pages=481–490 |doi=10.1007/s00384-018-3203-7 |pmid=30607579 |s2cid=57427824 |issn=1432-1262}}</ref> For people with localized cancer, the preferred treatment is complete surgical removal with adequate [[Resection margin|margins]], with the attempt of achieving a cure.<!-- <ref name=Lancet10/> --> The procedure of choice is a partial [[colectomy]] (or proctocolectomy for rectal lesions) where the affected part of the colon or rectum is removed along with parts of its [[mesocolon]] and [[Mesenteric arteries|blood supply]] to facilitate removal of draining [[lymph node]]s. This can be done either by an open [[laparotomy]] or [[laparoscopic]]ally, depending on factors related to the individual person and lesion factors.<ref name="Lancet10" /> The colon may then be reconnected or a person may have a [[colostomy]].<ref name=NCI2014PtTx/>

If there are only a few metastases in the liver or lungs, these may also be removed.<!-- <ref name=Lancet10/> --> [[Chemotherapy]] may be used before surgery to shrink the cancer before attempting to remove it.<!-- <ref name=Lancet10/> --> The two most common sites of recurrence of colorectal cancer are the [[liver]] and [[lungs]].<ref name=Lancet10/> For [[peritoneal carcinomatosis]] [[cytoreductive surgery]], sometimes in combination with [[Hyperthermic intraperitoneal chemotherapy|HIPEC]] can be used in an attempt to remove the cancer.<ref name="McCarthy-2012" />

===Chemotherapy===
In both cancer of the [[colon (anatomy)|colon]] and [[rectum]], [[chemotherapy]] may be used in addition to surgery in certain cases. The decision to add chemotherapy in management of colon and rectal cancer depends on the stage of the disease.<ref name="Colorectal Colon Cancer">{{cite web |url=https://my.clevelandclinic.org/health/diseases/14501-colorectal-colon-cancer| title=Colorectal (Colon) Cancer
|website=Cleveland Clinic |access-date= 9 July 2021}}</ref>

In Stage I colon cancer, no chemotherapy is offered, and surgery is the definitive treatment. The role of chemotherapy in Stage II colon cancer is debatable, and is usually not offered unless risk factors such as T4 tumor, undifferentiated tumor, vascular and perineural invasion or inadequate lymph node sampling is identified.<ref>{{cite journal | vauthors = Böckelman C, Engelmann BE, Kaprio T, Hansen TF, Glimelius B | title = Risk of recurrence in patients with colon cancer stage II and III: a systematic review and meta-analysis of recent literature | journal = Acta Oncologica | volume = 54 | issue = 1 | pages = 5–16 | date = January 2015 | pmid = 25430983 | doi = 10.3109/0284186x.2014.975839 | doi-access = free }}</ref> It is also known that the people who carry abnormalities of the mismatch repair genes do not benefit from chemotherapy. For Stage III and Stage IV colon cancer, chemotherapy is an integral part of treatment.<ref name=Lancet10/>

If cancer has spread to the [[lymph nodes]] or distant organs, which is the case with Stage III and Stage IV colon cancer respectively, adding chemotherapy agents [[fluorouracil]], [[capecitabine]] or [[oxaliplatin]] increases life expectancy.<!-- <ref name=Lancet10/> --> If the lymph nodes do not contain cancer, the benefits of chemotherapy are controversial.<!-- <ref name=Lancet10/> --> If the cancer is widely metastatic or unresectable, treatment is then [[palliative]].<!-- <ref name=Lancet10/> --> Typically in this setting, a number of different chemotherapy medications may be used.<ref name="Lancet10" /> Chemotherapy drugs for this condition may include [[capecitabine]], [[fluorouracil]], [[irinotecan]], [[oxaliplatin]] and [[Tegafur-Uracil|UFT]].<ref>{{cite journal | vauthors =  | title = Chemotherapy of metastatic colorectal cancer | journal = Prescrire International | volume = 19 | issue = 109 | pages = 219–224 | date = October 2010 | pmid = 21180382 }}</ref> The drugs capecitabine and fluorouracil are interchangeable, with capecitabine being an oral medication and fluorouracil being an intravenous medicine. Some specific [[chemotherapy regimen|regimen]]s used for CRC are [[CAPOX]], [[FOLFOX]], [[FOLFOXIRI]], and [[FOLFIRI]].<ref name="Fakih">{{cite journal | vauthors = Fakih MG | title = Metastatic colorectal cancer: current state and future directions | journal = Journal of Clinical Oncology | volume = 33 | issue = 16 | pages = 1809–1824 | date = June 2015 | pmid = 25918280 | doi = 10.1200/JCO.2014.59.7633 | ref = 10.1200/JCO.2014.59.7633 | doi-access = free }}</ref> Antiangiogenic drugs such as [[bevacizumab]] are often added in first line therapy.<ref name="l758">{{cite journal | last=Bendell | first=Johanna | title=Antiangiogenic Agents in First-Line and Second-Line Therapy for Advanced Colorectal Cancer | journal=Gastrointestinal Cancer Research | publisher=International Society of Gastrointestinal Oncology | volume=1 | issue=4 Suppl 2 | date=2024-03-14 | pages=S22-8 | pmid=19365574 | pmc=2666834 }}</ref> Another class of drugs used in the second line setting are [[epidermal growth factor receptor]] inhibitors, of which the three FDA approved ones are [[aflibercept]], [[cetuximab]] and [[panitumumab]].<ref name="Shaib2013">{{cite journal | vauthors = Shaib W, Mahajan R, El-Rayes B | title = Markers of resistance to anti-EGFR therapy in colorectal cancer | journal = Journal of Gastrointestinal Oncology | volume = 4 | issue = 3 | pages = 308–318 | date = September 2013 | pmid = 23997942 | pmc = 3712296 | doi = 10.3978/j.issn.2078-6891.2013.029 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yau TO | title = Precision treatment in colorectal cancer: Now and the future | journal = JGH Open | volume = 3 | issue = 5 | pages = 361–369 | date = October 2019 | pmid = 31633039 | pmc = 6788378 | doi = 10.1002/jgh3.12153 }}</ref>

The primary difference in the approach to low stage rectal cancer is the incorporation of radiation therapy. Often, it is used in conjunction with chemotherapy in a [[neoadjuvant]] fashion to enable surgical resection, so that ultimately a [[colostomy]] is not required. However, it may not be possible in low lying tumors, in which case, a permanent colostomy may be required. Stage IV rectal cancer is treated similar to Stage IV colon cancer.

Stage IV colorectal cancer due to [[peritoneal carcinomatosis]] can be treated using [[Hyperthermic intraperitoneal chemotherapy|HIPEC]] combined with cytoreductive surgery, in some people.<ref>{{cite journal | vauthors = Sugarbaker PH, Van der Speeten K | title = Surgical technology and pharmacology of hyperthermic perioperative chemotherapy | journal = Journal of Gastrointestinal Oncology | volume = 7 | issue = 1 | pages = 29–44 | date = February 2016 | pmid = 26941982 | pmc = 4754302 | doi = 10.3978/j.issn.2078-6891.2015.105 }}</ref><ref>{{cite journal | vauthors = Segura-Sampedro JJ, Morales-Soriano R | title = Prophylactic HIPEC with oxaliplatin might be of benefit in T4 and perforated colon cancer: another possible interpretation of the COLOPEC results | journal = Revista Espanola de Enfermedades Digestivas | volume = 112 | issue = 8 | pages = 666 | date = August 2020 | pmid = 32686435 | doi = 10.17235/reed.2020.6755/2019 | doi-access = free | hdl = 20.500.13003/12309 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Esquivel J, Sticca R, Sugarbaker P, Levine E, Yan TD, Alexander R, Baratti D, Bartlett D, Barone R, Barrios P, Bieligk S, Bretcha-Boix P, Chang CK, Chu F, Chu Q, Daniel S, de Bree E, Deraco M, Dominguez-Parra L, Elias D, Flynn R, Foster J, Garofalo A, Gilly FN, Glehen O, Gomez-Portilla A, Gonzalez-Bayon L, Gonzalez-Moreno S, Goodman M, Gushchin V, Hanna N, Hartmann J, Harrison L, Hoefer R, Kane J, Kecmanovic D, Kelley S, Kuhn J, Lamont J, Lange J, Li B, Loggie B, Mahteme H, Mann G, Martin R, Misih RA, Moran B, Morris D, Onate-Ocana L, Petrelli N, Philippe G, Pingpank J, Pitroff A, Piso P, Quinones M, Riley L, Rutstein L, Saha S, Alrawi S, Sardi A, Schneebaum S, Shen P, Shibata D, Spellman J, Stojadinovic A, Stewart J, Torres-Melero J, Tuttle T, Verwaal V, Villar J, Wilkinson N, Younan R, Zeh H, Zoetmulder F, Sebbag G | title = Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology | journal = Annals of Surgical Oncology | volume = 14 | issue = 1 | pages = 128–133 | date = January 2007 | pmid = 17072675 | doi = 10.1245/s10434-006-9185-7 | s2cid = 21282326 }}</ref> Also, T4 colorectal cancer can be treated with HIPEC to avoid future relapses.<ref>{{cite journal | vauthors = Arjona-Sánchez A, Espinosa-Redondo E, Gutiérrez-Calvo A, Segura-Sampedro JJ, Pérez-Viejo E, Concepción-Martín V, Sánchez-García S, García-Fadrique A, Prieto-Nieto I, Barrios-Sanchez P, Torres-Melero J, Ramírez Faraco M, Prada-Villaverde A, Carrasco-Campos J, Artiles-Armas M, Villarejo-Campos P, Ortega-Pérez G, Boldo-Roda E, Sánchez-Hidalgo JM, Casado-Adam A, Rodríguez-Ortiz L, Aranda E, Cano-Osuna MT, Díaz-López C, Romero-Ruiz A, Briceño-Delgado J, Rufián-Peña S | title = Efficacy and Safety of Intraoperative Hyperthermic Intraperitoneal Chemotherapy for Locally Advanced Colon Cancer: A Phase 3 Randomized Clinical Trial | journal = JAMA Surgery | date = April 2023 | volume = 158 | issue = 7 | pages = 683–691 | pmid = 37099280 | pmc = 10134040 | doi = 10.1001/jamasurg.2023.0662 }}</ref>

===Radiation therapy===
While a combination of [[radiation]] and chemotherapy may be useful for [[rectal cancer]],<ref name=Lancet10/> for some people requiring treatment, chemoradiotherapy can increase acute treatment-related toxicity, and has not been shown to improve survival rates compared to radiotherapy alone, although it is associated with less local recurrence.<ref name="McCarthy-2012">{{cite journal | vauthors = McCarthy K, Pearson K, Fulton R, Hewitt J | title = Pre-operative chemoradiation for non-metastatic locally advanced rectal cancer | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD008368 | date = December 2012 | pmid = 23235660 | doi = 10.1002/14651858.CD008368.pub2 | collaboration = Cochrane Colorectal Cancer Group }}</ref> For squamous cell carcinoma of the anal canal, chemoradiation therapy (CRT) with 5-FU and mitomycin C is preferred over radiation alone, offering improved survival outcomes but with increased risks of [[Hematologic disease|acute hematological toxicity]].<ref name="djae195">{{Cite journal |last1=Troester |first1=Alexander |last2=Parikh |first2=Romil |last3=Southwell |first3=Bronwyn |last4=Ester |first4=Elizabeth |last5=Sultan |first5=Shahnaz |last6=Greeno |first6=Edward |last7=Arsoniadis |first7=Elliot |last8=Church |first8=Timothy R |last9=Wilt |first9=Timothy |last10=Butler |first10=Mary |last11=Goffredo |first11=Paolo |date=2024-08-20 |title=Treatment of stage I-III squamous cell anal cancer: a comparative effectiveness systematic review |url=https://academic.oup.com/jnci/advance-article/doi/10.1093/jnci/djae195/7737475 |journal=JNCI: Journal of the National Cancer Institute |pages=djae195 |language=en |doi=10.1093/jnci/djae195 |pmid=39163501 |issn=0027-8874}}</ref> 

The use of radiotherapy in colon cancer is not routine due to the sensitivity of the bowels to radiation.<ref>{{cite book| vauthors = DeVita VT, Lawrence TS, Rosenberg SA |title=DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology|url=https://books.google.com/books?id=NF90HzUFPjgC&pg=PA1258|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-7207-5|pages=1258–}}</ref> Radiation therapy's side effects (and occurrence rates) include acute (27%) and late (17%) [[Skin condition|dermatological toxicities]], acute (14%) and late (27%) [[Gastrointestinal disease|gastrointestinal toxicities]],<ref name="djae195" /> and late [[Radiation enteropathy|pelvic radiation disease]] (1-10%), e.g., [[Radiation-induced lumbar plexopathy|irreversible lumbosacral plexopathy]].<ref name="CCR-19-2744">{{cite journal |last1=Huh |first1=Jung Wook |last2=Tanksley |first2=Jarred |last3=Chino |first3=Junzo |last4=Willett |first4=Christopher G. |last5=Dewhirst |first5=Mark W. |title=Long-term Consequences of Pelvic Irradiation: Toxicities, Challenges, and Therapeutic Opportunities with Pharmacologic Mitigators |journal=Clinical Cancer Research |date=July 1, 2020 |volume=26 |issue=13 |pages=3079–3090 |doi=10.1158/1078-0432.CCR-19-2744 |pmid=32098770 |url=https://aacrjournals.org/clincancerres/article/26/13/3079/82622/Long-term-Consequences-of-Pelvic-Irradiation |access-date=24 October 2024 |issn=1078-0432}}</ref>

As with chemotherapy, radiotherapy can be used as a neoadjuvant for clinical stages T3 and T4 for rectal cancer.<ref name="Neoadjuvant radiotherapy for rectal">{{cite journal | vauthors = Feeney G, Sehgal R, Sheehan M, Hogan A, Regan M, Joyce M, Kerin M | title = Neoadjuvant radiotherapy for rectal cancer management | journal = World Journal of Gastroenterology | volume = 25 | issue = 33 | pages = 4850–4869 | date = September 2019 | pmid = 31543678 | pmc = 6737323 | doi = 10.3748/wjg.v25.i33.4850 | doi-access = free }}</ref> This results in downsizing or downstaging of the tumour, preparing it for surgical resection, and also decreases local recurrence rates.<ref name="Neoadjuvant radiotherapy for rectal" /> For locally advanced rectal cancer, neoadjuvant chemoradiotherapy has become the standard treatment.<ref>{{cite journal | vauthors = Li Y, Wang J, Ma X, Tan L, Yan Y, Xue C, Hui B, Liu R, Ma H, Ren J | title = A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer | journal = International Journal of Biological Sciences | volume = 12 | issue = 8 | pages = 1022–1031 | year = 2016 | pmid = 27489505 | pmc = 4971740 | doi = 10.7150/ijbs.15438 }}</ref> Additionally, when surgery is not possible radiation therapy has been suggested to be an effective treatment against CRC pulmonary metastases, which are developed by 10-15% of people with CRC.<ref>{{cite journal | vauthors = Cao C, Wang D, Tian DH, Wilson-Smith A, Huang J, Rimner A | title = A systematic review and meta-analysis of stereotactic body radiation therapy for colorectal pulmonary metastases | journal = Journal of Thoracic Disease | volume = 11 | issue = 12 | pages = 5187–5198 | date = December 2019 | pmid = 32030236 | pmc = 6988072 | doi = 10.21037/jtd.2019.12.12 | doi-access = free }}</ref>

=== Immunotherapy ===
[[Immunotherapy]] with immune checkpoint inhibitors has been found to be useful for a type of colorectal cancer with [[mismatch repair deficiency]] and [[microsatellite instability]].<ref name="Bo2017">{{cite journal | vauthors = Boland PM, Ma WW | title = Immunotherapy for Colorectal Cancer | journal = Cancers | volume = 9 | issue = 5 | pages = 50 | date = May 2017 | pmid = 28492495 | pmc = 5447960 | doi = 10.3390/cancers9050050 | doi-access = free }}</ref><ref name="Nic2017">{{cite journal | vauthors = Syn NL, Teng MW, Mok TS, Soo RA | title = De-novo and acquired resistance to immune checkpoint targeting | journal = The Lancet. Oncology | volume = 18 | issue = 12 | pages = e731–e741 | date = December 2017 | pmid = 29208439 | doi = 10.1016/s1470-2045(17)30607-1 }}</ref><ref name="Borras2023">{{cite journal | vauthors = Borras, DM, Verbandt, S, Ausserhofer, M et al. | title = Single cell dynamics of tumor specificity vs bystander activity in CD8+ T cells define the diverse immune landscapes in colorectal cancer | journal = Cell Discovery | volume = 9 | issue = 114 | pages = 114 | date = November 2023 | pmid = 37968259 | doi = 10.1038/s41421-023-00605-4 | doi-access = free | pmc = 10652011 }}</ref> [[Pembrolizumab]] is approved for advanced CRC tumours that are MMR deficient and have failed usual treatments.<ref>{{cite web |title=FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication |url=https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm560040.htm |website=U.S. Food and Drug Administration|date=February 9, 2019 }}</ref> Most people who do improve, however, still worsen after months or years.<ref name=Nic2017/>

On the other hand, in a prospective phase 2 study published in June 2022 in The New England Journal of Medicine, 12 patients with Deficient Mismatch Repair ({{proper name|dMMR}}) stage II or III rectal adenocarcinoma were administered single-agent [[dostarlimab]], an anti–PD-1 monoclonal antibody, every three weeks for six months. After a median follow-up of 12 months (range, 6 to 25 months), all 12 patients had a complete clinical response with no evidence of tumor on MRI, 18F-fluorodeoxyglucose–positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. Moreover, no patient in the trial needed chemoradiotherapy or surgery, and no patient reported adverse events of grade 3 or higher. However, although the results of this study are promising, the study is small and has uncertainties about long-term outcomes.<ref name="dostarlimab 2022">{{cite journal | vauthors = Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, El Dika IH, Segal N, Shcherba M, Sugarman R, Stadler Z, Yaeger R, Smith JJ, Rousseau B, Argiles G, Patel M, Desai A, Saltz LB, Widmar M, Iyer K, Zhang J, Gianino N, Crane C, Romesser PB, Pappou EP, Paty P, Garcia-Aguilar J, Gonen M, Gollub M, Weiser MR, Schalper KA, Diaz LA Jr | title = PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer | journal = The New England Journal of Medicine | volume = 386 | issue = 25 | date = June 2022 | pages = 2363–2376 | pmid = 35660797 | doi = 10.1056/NEJMoa2201445 | pmc = 9492301 | s2cid = 249395846 }}</ref>

===Palliative care===
[[Palliative care]] can be used at the same time as the cancer treatment and is recommended for any person who has advanced colon cancer or who has significant symptoms.<ref>{{cite web|title=Palliative or Supportive Care|url=http://www.cancer.org/treatment/treatmentsandsideeffects/palliativecare/index|publisher=American Cancer Society|access-date=20 August 2014|url-status=live|archive-url=https://web.archive.org/web/20140821054618/http://www.cancer.org/treatment/treatmentsandsideeffects/palliativecare/index|archive-date=August 21, 2014|df=mdy-all}}</ref><ref>{{cite web|title=ASCO Provisional Clinical Opinion: The Integration of Palliative Care into Standard Oncology Care |url=http://www.asco.org/quality-guidelines/asco-provisional-clinical-opinion-integration-palliative-care-standard-oncology |publisher=ASCO |access-date=20 August 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140821114944/http://www.asco.org/quality-guidelines/asco-provisional-clinical-opinion-integration-palliative-care-standard-oncology |archive-date=August 21, 2014 |df=mdy }}</ref> Involvement of palliative care may be beneficial to improve the quality of life for both the person and his or her family, by improving symptoms, anxiety and preventing admissions to the hospital.<ref>{{cite journal | vauthors = Higginson IJ, Evans CJ | title = What is the evidence that palliative care teams improve outcomes for cancer patients and their families? | journal = Cancer Journal | volume = 16 | issue = 5 | pages = 423–435 | date = Sep–Oct 2010 | pmid = 20890138 | doi = 10.1097/PPO.0b013e3181f684e5 | s2cid = 39881122 | doi-access = free }}</ref>

In people with incurable colorectal cancer, palliative care can consist of procedures that relieve symptoms or complications from the cancer but do not attempt to cure the underlying cancer, thereby improving [[quality of life]]. Surgical options may include non-curative surgical removal of some of the cancer tissue, bypassing part of the intestines, or stent placement. These procedures can be considered to improve symptoms and reduce complications such as bleeding from the tumor, abdominal pain and intestinal obstruction.<ref>{{cite journal | vauthors = Wasserberg N, Kaufman HS | title = Palliation of colorectal cancer | journal = Surgical Oncology | volume = 16 | issue = 4 | pages = 299–310 | date = December 2007 | pmid = 17913495 | doi = 10.1016/j.suronc.2007.08.008 }}</ref> Non-operative methods of symptomatic treatment include radiation therapy to decrease tumor size as well as pain medications.<ref>{{cite journal | vauthors = Amersi F, Stamos MJ, Ko CY | title = Palliative care for colorectal cancer | journal = Surgical Oncology Clinics of North America | volume = 13 | issue = 3 | pages = 467–477 | date = July 2004 | pmid = 15236729 | doi = 10.1016/j.soc.2004.03.002 }}</ref>

=== Psychosocial Intervention ===
In addition to medical intervention, a variety of psychosocial interventions have been implemented to address psychosocial concerns in the context of colorectal cancer.<ref name="Son-2018">{{Cite journal |last1=Son |first1=Heesook |last2=Son |first2=Youn-Jung |last3=Kim |first3=Hyerang |last4=Lee |first4=Yoonju |date=2018-06-08 |title=Effect of psychosocial interventions on the quality of life of patients with colorectal cancer: a systematic review and meta-analysis |journal=Health and Quality of Life Outcomes |volume=16 |issue=1 |pages=119 |doi=10.1186/s12955-018-0943-6 |doi-access=free |issn=1477-7525 |pmc=5994008 |pmid=29884182}}</ref> Depression and anxiety are highly prevalent in patients diagnosed with CRC, therefore psychosocial interventions can be helpful for alleviating psychological distress.<ref name="Peng-2019">{{Cite journal |last1=Peng |first1=Yu-Ning |last2=Huang |first2=Mei-Li |last3=Kao |first3=Chia-Hung |date=2019-01-31 |title=Prevalence of Depression and Anxiety in Colorectal Cancer Patients: A Literature Review |journal=International Journal of Environmental Research and Public Health |language=en |volume=16 |issue=3 |pages=411 |doi=10.3390/ijerph16030411 |doi-access=free |issn=1660-4601 |pmc=6388369 |pmid=30709020}}</ref><ref name="auto1">{{Cite journal |last1=Cheng |first1=Vicki |last2=Oveisi |first2=Niki |last3=McTaggart-Cowan |first3=Helen |last4=Loree |first4=Jonathan M. |last5=Murphy |first5=Rachel A. |last6=De Vera |first6=Mary A. |date=2022 |title=Colorectal Cancer and Onset of Anxiety and Depression: A Systematic Review and Meta-Analysis |journal=Current Oncology |language=en |volume=29 |issue=11 |pages=8751–8766 |doi=10.3390/curroncol29110689 |doi-access=free |issn=1718-7729 |pmc=9689519 |pmid=36421342}}</ref> Many patients continue to experience symptoms of anxiety and depression following treatment, regardless of treatment outcome.<ref name="Peng-2019" /><ref>{{Cite journal |last1=Mosher |first1=Catherine E. |last2=Winger |first2=Joseph G. |last3=Given |first3=Barbara A. |last4=Helft |first4=Paul R. |last5=O'Neil |first5=Bert H. |date=2016 |title=Mental health outcomes during colorectal cancer survivorship: a review of the literature: Mental health in colorectal cancer survivorship |journal=Psycho-Oncology |language=en |volume=25 |issue=11 |pages=1261–1270 |doi=10.1002/pon.3954 |pmc=4894828 |pmid=26315692}}</ref> Societal stigmas associated with colorectal cancer present further psychosocial challenges for CRC patients and their families.<ref name="Reynolds-2013">{{Cite journal |last1=Reynolds |first1=Lisa M. |last2=Consedine |first2=Nathan S. |last3=Pizarro |first3=David A. |last4=Bissett |first4=Ian P. |date=2013 |title=Disgust and Behavioral Avoidance in Colorectal Cancer Screening and Treatment: A Systematic Review and Research Agenda |url=https://journals.lww.com/00002820-201304000-00006 |journal=Cancer Nursing |language=en |volume=36 |issue=2 |pages=122–130 |doi=10.1097/NCC.0b013e31826a4b1b |pmid=23047793 |issn=0162-220X}}</ref><ref name="Phelan-2013a">{{Cite journal |last1=Phelan |first1=Sean M. |last2=Griffin |first2=Joan M. |last3=Jackson |first3=George L. |last4=Zafar |first4=S. Yousuf |last5=Hellerstedt |first5=Wendy |last6=Stahre |first6=Mandy |last7=Nelson |first7=David |last8=Zullig |first8=Leah L. |last9=Burgess |first9=Diana J. |last10=van Ryn |first10=Michelle |date=2013 |title=Stigma, perceived blame, self-blame, and depressive symptoms in men with colorectal cancer |journal=Psycho-Oncology |language=en |volume=22 |issue=1 |pages=65–73 |doi=10.1002/pon.2048 |issn=1057-9249 |pmc=6000725 |pmid=21954081}}</ref>

==== Depression and Anxiety ====
Colorectal cancer patients have a 51% higher risk of experiencing depression than individuals without the disease.<ref name="auto1"/> Additionally, CRC patients are at high risk of experiencing severe anxiety, low self-esteem, poor self-concept, and social anxiety.<ref name="Peng-2019"/><ref name="auto2">{{Cite journal |last1=Hoon |first1=Lim Siew |last2=Chi Sally |first2=Chan Wai |last3=Hong-Gu |first3=He |date=2013 |title=Effect of psychosocial interventions on outcomes of patients with colorectal cancer: A review of the literature |url=http://dx.doi.org/10.1016/j.ejon.2013.05.001 |journal=European Journal of Oncology Nursing |volume=17 |issue=6 |pages=883–891 |doi=10.1016/j.ejon.2013.05.001 |pmid=23759360 |issn=1462-3889}}</ref>

==== Post-Treatment Distress ====
Regardless of treatment outcome, many CRC patients experience ongoing symptoms of anxiety, depression, and distress.<ref name="Peng-2019"/>

Survivorship of CRC can involve significant lifestyle adjustments.<ref name="Phelan-2013a"/> Postoperative afflictions may include stomas, bowel issues, incontinence, odor, and changes to sexual functioning.<ref name="Phelan-2013a" /><ref name="auto2"/> These changes can result in distorted body image, social anxiety, depression, and distress—all of which contribute to a poorer quality of life.<ref name="Phelan-2013a" /><ref>{{Cite journal |last1=Meng |first1=Xinyu |last2=Wang |first2=Xiaodong |last3=Dong |first3=Zaiquan |date=2021-10-01 |title=Impact of non-pharmacological interventions on quality of life, anxiety, and depression scores in patients with colorectal cancer: a systematic review and meta-analysis of randomized controlled trials |url=https://doi.org/10.1007/s00520-021-06185-x |journal=Supportive Care in Cancer |language=en |volume=29 |issue=10 |pages=5635–5652 |doi=10.1007/s00520-021-06185-x |pmid=33786669 |issn=1433-7339}}</ref>

Colorectal cancer is the second leading cause of cancer-related death worldwide.<ref name="auto">{{Cite journal |last1=Hua |first1=Hongmei |last2=Jiang |first2=Qiuping |last3=Sun |first3=Pan |last4=Xu |first4=Xing |date=2023-05-05 |title=Risk factors for early-onset colorectal cancer: systematic review and meta-analysis |journal=Frontiers in Oncology |volume=13 |doi=10.3389/fonc.2023.1132306 |doi-access=free |pmid=37213277 |pmc=10196487 |issn=2234-943X}}</ref> Transitioning into palliative care and contending with mortality can be a deeply distressing experience for a CRC patient and their loved ones.

==== Stigma ====
Colorectal cancer is highly stigmatized and can elicit feelings of disgust from  patients, healthcare professionals, family, intimate partners, and the general public.<ref name="Reynolds-2013"/> Patients with stomas are especially vulnerable to stigmatization due to unavoidable odors, gas, and unpleasant noises from stoma bags.<ref name="Reynolds-2013" /> Additionally, associated CRC risk factors like poor diet, alcohol consumption, and lack of physical activity prompt negative assumptions of blame and personal responsibility onto CRC patients.<ref name="Phelan-2013a"/> Judgement from others along with internalized self-blame and embarrassment can negatively affect self-esteem, sociability, and quality of life.<ref name="Phelan-2013a" />

==== Methods of Intervention ====
Face-to-face interventions such as clinician-patient talk therapy, body-mind-spirit practices, and support group sessions have been identified as most effective in reducing anxiety and depression in CRC patients.<ref name="Son-2018"/> Additionally, journaling exercises and over-the-phone talk therapy sessions have been implemented.<ref name="Son-2018" /> Though deemed less effective, these non-face-to-face interventions are economically inclusive and have been found to reduce both depression and anxiety in CRC patients.<ref name="Son-2018" />

===Follow-up===

The U.S. [[National Comprehensive Cancer Network]] and [[American Society of Clinical Oncology]] provide guidelines for the follow-up of colon cancer.<ref name="NCCNguidelines">{{cite web|url=http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf|title=National Comprehensive Cancer Network|work=nccn.org|url-status=live|archive-url=https://web.archive.org/web/20090325235446/http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf|archive-date=March 25, 2009|df=mdy-all}}</ref><ref name="pmid16260687">{{cite journal | vauthors = Desch CE, Benson AB, Somerfield MR, Flynn PJ, Krause C, Loprinzi CL, Minsky BD, Pfister DG, Virgo KS, Petrelli NJ | title = Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline | journal = Journal of Clinical Oncology | volume = 23 | issue = 33 | pages = 8512–8519 | date = November 2005 | pmid = 16260687 | doi = 10.1200/JCO.2005.04.0063 | doi-access = free }}</ref> A [[medical history]] and [[physical examination]] are recommended every 3 to 6 months for 2 years, then every 6 months for 5 years. [[Carcinoembryonic antigen]] blood level measurements follow the same timing, but are only advised for people with T2 or greater lesions who are candidates for intervention. A [[Computed tomography|CT-scan]] of the chest, abdomen and pelvis can be considered annually for the first 3 years for people who are at high risk of recurrence (for example, those who had poorly differentiated tumors or venous or lymphatic invasion) and are candidates for curative surgery (with the aim to cure). A [[colonoscopy]] can be done after 1 year, except if it could not be done during the initial staging because of an obstructing mass, in which case it should be performed after 3 to 6 months. If a villous polyp, a polyp >1 centimeter or high-grade dysplasia is found, it can be repeated after 3 years, then every 5 years. For other abnormalities, the colonoscopy can be repeated after 1 year.<ref name="Colorectal Colon Cancer"/>

Routine [[Positron emission tomography|PET]] or [[Medical ultrasonography|ultrasound scanning]], [[chest X-ray]]s, [[complete blood count]] or [[liver function tests]] are not recommended.<ref name="NCCNguidelines"/><ref name="pmid16260687"/>

For people who have undergone curative surgery or adjuvant therapy (or both) to treat non-metastatic colorectal cancer, intense surveillance and close follow-up have not been shown to provide additional survival benefits.<ref>{{cite journal | vauthors = Jeffery M, Hickey BE, Hider PN | title = Follow-up strategies for patients treated for non-metastatic colorectal cancer | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 9 | pages = CD002200 | date = September 2019 | pmid = 31483854 | pmc = 6726414 | doi = 10.1002/14651858.CD002200.pub4 }}</ref>

===Exercise===
Exercise may be recommended in the future as secondary therapy to cancer survivors. In epidemiological studies, exercise may decrease colorectal cancer-specific mortality and all-cause mortality. Results for the specific amounts of exercise needed to observe a benefit were conflicting. These differences may reflect differences in tumour biology and the expression of biomarkers. People with tumors that lacked [[CTNNB1]] expression (β-catenin), involved in [[Wnt signalling pathway]], required more than 18 [[Metabolic equivalent]] (MET) hours per week, a measure of exercise, to observe a reduction in colorectal cancer mortality. The mechanism of how exercise benefits survival may be involved in immune surveillance and inflammation pathways. In clinical studies, a pro-inflammatory response was found in people with stage II-III colorectal cancer who underwent 2 weeks of moderate exercise after completing their primary therapy. Oxidative balance may be another possible mechanism for benefits observed. A significant decrease in 8-oxo-dG was found in the urine of people who underwent 2 weeks of moderate exercise after primary therapy. Other possible mechanisms may involve metabolic hormone and sex-steroid hormones, although these pathways may be involved in other types of cancers.<ref>{{cite journal | vauthors = Betof AS, Dewhirst MW, Jones LW | title = Effects and potential mechanisms of exercise training on cancer progression: a translational perspective | journal = Brain, Behavior, and Immunity | volume = 30 | issue = Suppl | pages = S75–S87 | date = March 2013 | pmid = 22610066 | pmc = 3638811 | doi = 10.1016/j.bbi.2012.05.001 }}</ref><ref name="Ballard-Barbash2012">{{cite journal | vauthors = Ballard-Barbash R, Friedenreich CM, Courneya KS, Siddiqi SM, McTiernan A, Alfano CM | title = Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review | journal = Journal of the National Cancer Institute | volume = 104 | issue = 11 | pages = 815–840 | date = June 2012 | pmid = 22570317 | pmc = 3465697 | doi = 10.1093/jnci/djs207 }}</ref>

Another potential biomarker may be [[p27 (gene)|p27]]. Survivors with tumors that expressed p27 and performed greater and equal to 18 MET hours per week were found to have reduced colorectal cancer mortality survival compared to those with less than 18 MET hours per week. Survivors without p27 expression who exercised were shown to have worse outcomes. The constitutive activation of [[PI3K/AKT/mTOR pathway]] may explain the loss of p27 and excess energy balance may up-regulate p27 to stop cancer cells from dividing.<ref name="Ballard-Barbash2012"/>

Physical activity provides benefits to people with non-advanced colorectal cancer. Improvements in aerobic fitness, cancer-related fatigue and health-related quality of life have been reported in the short term.<ref name="Physical activity interventions for">{{cite journal | vauthors = McGettigan M, Cardwell CR, Cantwell MM, Tully MA | title = Physical activity interventions for disease-related physical and mental health during and following treatment in people with non-advanced colorectal cancer | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 5 | pages = CD012864 | date = May 2020 | pmid = 32361988 | pmc = 7196359 | doi = 10.1002/14651858.cd012864.pub2 }}</ref> However, these improvements were not observed at the level of disease-related mental health, such as anxiety and depression.<ref name="Physical activity interventions for"/>

==Prognosis==
Fewer than 600 genes are linked to outcomes in colorectal cancer.<ref name="Uh2017">{{cite journal | vauthors = Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z, Edfors F, Sanli K, von Feilitzen K, Oksvold P, Lundberg E, Hober S, Nilsson P, Mattsson J, Schwenk JM, Brunnström H, Glimelius B, Sjöblom T, Edqvist PH, Djureinovic D, Micke P, Lindskog C, Mardinoglu A, Ponten F | title = A pathology atlas of the human cancer transcriptome | journal = Science | volume = 357 | issue = 6352 | pages = eaan2507 | date = August 2017 | pmid = 28818916 | doi = 10.1126/science.aan2507 | doi-access = free }}</ref> These include both unfavorable genes, where high expression is related to poor outcome, for example the [[HSPA1A|heat shock 70 kDa protein 1 (HSPA1A)]], and favorable genes where high expression is associated with better survival, for example the [[RBM3|putative RNA-binding protein 3 (RBM3)]].<ref name=Uh2017/> The prognosis is also correlated with a poor fidelity of the pre-mRNA splicing apparatus, and thus a high number of deviating alternative splicing.<ref name="Stromme">{{cite journal | vauthors = Strømme JM, Johannessen B, Skotheim RI | title = Deviating alternative splicing as a molecular subtype of microsatellite stable colorectal cancer | journal = JCO Clinical Cancer Informatics | volume = 7 | pages = e2200159 | date = 2023 | issue = 7 | pmid = 36821799 | doi = 10.1200/CCI.22.00159 | doi-access = free | hdl = 10852/108838 | hdl-access = free }}</ref>

===Recurrence rates===
{{Main|Cancer recurrence#Rectal cancer}}
The average five-year recurrence rate in people with ''colon cancer'' where surgery is successful is 5% for [[Cancer staging|stage]] I cancers, 12% in stage II and 33% in stage III. However, depending on the number of risk factors it ranges from 9–22% in stage II and 17–44% in stage III.<ref>{{cite journal | vauthors = Osterman E, Glimelius B | title = Recurrence Risk After Up-to-Date Colon Cancer Staging, Surgery, and Pathology: Analysis of the Entire Swedish Population | journal = Diseases of the Colon and Rectum | volume = 61 | issue = 9 | pages = 1016–1025 | date = September 2018 | pmid = 30086050 | doi = 10.1097/dcr.0000000000001158 | s2cid = 51934598 | url = http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-357138 }}</ref> The average five-year recurrence rate in people with ''rectal cancer'' where surgery is successful is 9% for stage 0 [[Neoadjuvant therapy|(after pre-treatment)]] cancers, 8% for stage I cancers, 18% in stage II and 34% in stage III. Depending on the number of risk factors (0-2) the risk for distant metastasis in ''rectal cancer'' ranges from 4-11% in stage 0, 6-12% in stage I, 11-28% in stage II and 15-43% in stage III.<ref name=":0">{{Cite journal |last1=Doroudian |first1=Sepehr |last2=Osterman |first2=Erik |last3=Glimelius |first3=Bengt |date=2024-06-09 |title=Risk Factors for Recurrence After Surgery for Rectal Cancer in a Modern, Nationwide Population-Based Cohort |journal=Annals of Surgical Oncology |volume=31 |issue=9 |pages=5570–5584 |language=en |doi=10.1245/s10434-024-15552-x |pmid=38853216 |issn=1068-9265|doi-access=free |pmc=11300512 }}</ref>

The recurrence rates have decreased over the past decades as a result of improvements in the colorectal cancer management.<ref>{{cite journal |last1=Nors |first1=Jesper |last2=Iversen |first2=Lene Hjerrild |last3=Erichsen |first3=Rune |last4=Gotschalck |first4=Kåre Andersson |last5=Andersen |first5=Claus Lindbjerg |title=Incidence of Recurrence and Time to Recurrence in Stage I to III Colorectal Cancer: A Nationwide Danish Cohort Study |journal=JAMA Oncology |date=1 January 2024 |volume=10 |issue=1 |pages=54–62 |doi=10.1001/jamaoncol.2023.5098 |pmid=37971197 |issn=2374-2437|pmc=10654928 }}</ref> The risk of recurrence after five years of surveillance remain very low.<ref>{{cite journal |last1=Nors |first1=J |last2=Gotschalck |first2=KA |last3=Erichsen |first3=R |last4=Andersen |first4=CL |title=Incidence of late recurrence and second primary cancers 5-10 years after non-metastatic colorectal cancer. |journal=International Journal of Cancer |date=1 June 2024 |volume=154 |issue=11 |pages=1890–1899 |doi=10.1002/ijc.34871 |pmid=38323453 |doi-access=free }}</ref>

===Survival rates===
In Europe the [[five-year survival rate]] for colorectal cancer is less than 60%.<!--<ref name=Lancet10/>--> In the [[developed world]] about a third of people who get the disease die from it.<ref name="Lancet10" />

Survival is directly related to detection and the type of cancer involved, but overall is poor for symptomatic cancers, as they are typically quite advanced. Survival rates for early stage detection are about five times that of late stage cancers. People with a tumor that has not breached the [[muscularis mucosa]] (TNM stage Tis, N0, M0) have a five-year survival rate of 100%, while those with invasive cancer of T1 (within the submucosal layer) or T2 (within the muscular layer) have an average five-year survival rate of approximately 90%. Those with a more invasive tumor yet without node involvement (T3-4, N0, M0) have an average five-year survival rate of approximately 70%. People with positive regional lymph nodes (any T, N1-3, M0) have an average five-year survival rate of approximately 40%, while those with distant metastases (any T, any N, M1) have a poor prognosis and the five year survival ranges from <5 percent to 31 percent.<ref name="pmid20332485">{{cite journal | vauthors = Zacharakis M, Xynos ID, Lazaris A, Smaro T, Kosmas C, Dokou A, Felekouras E, Antoniou E, Polyzos A, Sarantonis J, Syrios J, Zografos G, Papalambros A, Tsavaris N | title = Predictors of survival in stage IV metastatic colorectal cancer | journal = Anticancer Research | volume = 30 | issue = 2 | pages = 653–660 | date = February 2010 | pmid = 20332485 | url = https://pubmed.ncbi.nlm.nih.gov/20332485 }}</ref><ref name="agabegi2nd">{{cite book | vauthors = Agabegi ED, Agabegi SS |title=Step-Up to Medicine (Step-Up Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year=2008 |isbn=978-0-7817-7153-5 |url-access=registration |url=https://archive.org/details/stepuptomedicine0000agab }}</ref><ref>{{cite journal | vauthors = Hong Y |title=Clinical study of colorectal cancer operation: Survival analysis |journal=Korean Journal of Clinical Oncology 2020 |date=30 June 2020 |volume=16 |issue=1 |pages=3–8 |doi=10.14216/kjco.20002 |pmid=36945303 |pmc=9942716 |doi-access=free }}</ref><ref>{{cite web |title=Five-Year Survival Rates |url=https://training.seer.cancer.gov/colorectal/intro/survival.html |website=National Cancer Institute |access-date=9 May 2021}}</ref><ref>{{cite journal | vauthors = Xu Z, Becerra AZ, Fleming FJ, Aquina CT, Dolan JG, Monson JR, Temple LK, Jusko TA | title = Treatments for Stage IV Colon Cancer and Overall Survival | journal = The Journal of Surgical Research | volume = 242 | pages = 47–54 | date = October 2019 | pmid = 31071604 | doi = 10.1016/j.jss.2019.04.034 | s2cid = 149443256 }}</ref>

[[Survival rate|Five-year overall survival (OS)]] in rectal cancer after modern [[Neoadjuvant therapy|preoperative treatment]] and surgery was 90% for stage 0, 86% for stage I, 78% for stage II, and 67% for stage III according to a nationwide, population-based study.<ref name=":0" />

Whilst the impact of colorectal cancer on those who survive varies greatly there will often be a need to adapt to both physical and psychological outcomes of the illness and its treatment.<ref>{{cite journal | vauthors = Drageset S, Lindstrøm TC, Underlid K | title = "I just have to move on": Women's coping experiences and reflections following their first year after primary breast cancer surgery | language = English | journal = European Journal of Oncology Nursing | volume = 21 | pages = 205–211 | date = April 2016 | pmid = 26521054 | doi = 10.1016/j.ejon.2015.10.005 }}</ref> For example, it is common for people to experience incontinence,<ref>{{cite journal | vauthors = Restivo A, Zorcolo L, D'Alia G, Cocco F, Cossu A, Scintu F, Casula G | title = Risk of complications and long-term functional alterations after local excision of rectal tumors with transanal endoscopic microsurgery (TEM) | journal = International Journal of Colorectal Disease | volume = 31 | issue = 2 | pages = 257–266 | date = February 2016 | pmid = 26298182 | doi = 10.1007/s00384-015-2371-y | s2cid = 29087556 }}</ref> sexual dysfunction,<ref>{{cite journal | vauthors = Bregendahl S, Emmertsen KJ, Lindegaard JC, Laurberg S | title = Urinary and sexual dysfunction in women after resection with and without preoperative radiotherapy for rectal cancer: a population-based cross-sectional study | journal = Colorectal Disease | volume = 17 | issue = 1 | pages = 26–37 | date = January 2015 | pmid = 25156386 | doi = 10.1111/codi.12758 | s2cid = 42069306 }}</ref> problems with stoma care<ref>{{cite journal | vauthors = Ramirez M, McMullen C, Grant M, Altschuler A, Hornbrook MC, Krouse RS | title = Figuring out sex in a reconfigured body: experiences of female colorectal cancer survivors with ostomies | journal = Women & Health | volume = 49 | issue = 8 | pages = 608–624 | date = December 2009 | pmid = 20183104 | pmc = 2836795 | doi = 10.1080/03630240903496093 | first8 = Robert S. Krouse | first6 = Andrea Altschuler | first7 = Mark C. Hornbrook }}</ref> and fear of cancer recurrence<ref>{{cite journal | vauthors = Steele N, Haigh R, Knowles G, Mackean M | title = Carcinoembryonic antigen (CEA) testing in colorectal cancer follow up: what do patients think? | journal = Postgraduate Medical Journal | volume = 83 | issue = 983 | pages = 612–614 | date = September 2007 | pmid = 17823231 | pmc = 2600007 | doi = 10.1136/pgmj.2007.059634 }}</ref> after primary treatment has concluded.

A qualitative systematic review published in 2021 highlighted that there are three main factors influencing adaptation to living with and beyond colorectal cancer: support mechanisms, severity of late effects of treatment and psychosocial adjustment. Therefore, it is essential that people are offered appropriate support to help them better adapt to life following treatment.<ref>{{cite journal | vauthors = McGeechan GJ, Byrnes K, Campbell M, Carthy N, Eberhardt J, Paton W, Swainston K, Giles EL | title = A systematic review and qualitative synthesis of the experience of living with colorectal cancer as a chronic illness | journal = Psychology & Health | pages = 350–374 | date = January 2021 | volume = 37 | issue = 3 | pmid = 33499649 | doi = 10.1080/08870446.2020.1867137 | s2cid = 231771176 | url = https://research.tees.ac.uk/en/publications/a39a931d-36f0-4052-910b-3047b12a96c0 }}</ref>

==Epidemiology==
[[File:Colon and rectum cancers world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.3|Colon and rectum cancer deaths per million persons in 2012 {{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|3–17}}{{legend|#ffe820|18–21}}{{legend|#ffd820|22–27}}{{legend|#ffc020|28–36}}{{legend|#ffa020|37–54}}{{legend|#ff9a20|55–77}}{{legend|#f08015|78–162}}{{legend|#e06815|163–244}}{{legend|#d85010|245–329}}{{legend|#d02010|330–533}}{{div col end}}]]

Globally more than 1&nbsp;million people get colorectal cancer every year<ref name="Lancet10" /> resulting in about 715,000 deaths as of 2010 up from 490,000 in 1990.<ref>{{cite journal | vauthors = Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, etal | title = Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 | journal = Lancet | volume = 380 | issue = 9859 | pages = 2095–2128 | date = December 2012 | pmid = 23245604 | doi = 10.1016/S0140-6736(12)61728-0 | pmc = 10790329 | hdl-access = free | s2cid = 1541253 | hdl = 10536/DRO/DU:30050819 | url = http://www.cobiss.si/scripts/cobiss?command=DISPLAY&base=cobib&rid=1537267652&fmt=11 }}</ref>

{{As of|2012}}, it is the second most common cause of cancer in women (9.2% of diagnoses) and the third most common in men (10.0%)<ref name=WCR2014Epi/>{{rp|16}} with it being the fourth most common cause of cancer death after [[lung cancer|lung]], [[stomach cancer|stomach]], and [[liver cancer]].<ref name="WHO">{{cite web | last =WHO | author-link =World Health Organization | title =Cancer | publisher =World Health Organization | date =February 2010 | url =https://www.who.int/mediacentre/factsheets/fs297/en/ | access-date =January 5, 2011 | url-status =live | archive-url =https://web.archive.org/web/20101229092321/http://www.who.int/mediacentre/factsheets/fs297/en/ | archive-date =December 29, 2010 | df =mdy-all }}</ref> It is more common in developed than developing countries.<ref name="pmid20952724">{{cite journal | vauthors = Merika E, Saif MW, Katz A, Syrigos K, Syrigos C, Morse M | title = Review. Colon cancer vaccines: an update | journal = In Vivo | volume = 24 | issue = 5 | pages = 607–628 | date = 2010 | pmid = 20952724 }}</ref> Global incidence varies 10-fold, with highest rates in Australia, New Zealand, Europe and the US and lowest rates in Africa and South-Central Asia.<ref name="GLOBOCAN">{{cite web | url = http://globocan.iarc.fr/factsheet.asp | title = Colorectal Cancer Incidence, Mortality and Prevalence Worldwide in 2008 – Summary | archive-url = https://web.archive.org/web/20121017124937/http://globocan.iarc.fr/factsheet.asp | archive-date=October 17, 2012 | vauthors = Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM | date = 2010 }}; {{cite web | url =
http://globocan.iarc.fr | title = GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 | archive-url = https://web.archive.org/web/20110508055140/http://globocan.iarc.fr/ | archive-date=May 8, 2011 | location = Lyon, France | publisher = International Agency for Research on Cancer }}</ref>

===United States===
In 2022, the incidence of colorectal cancer in the United States was anticipated to be about 151,000 adults, including over 106,000 new cases of colon cancer (some 54,000 men and 52,000 women) and about 45,000 new cases of rectal cancer.<ref name="asco">{{cite web |title=Colorectal cancer: Statistics |url=https://www.cancer.net/cancer-types/colorectal-cancer/statistics |publisher=Cancer.net, American Society of Clinical Oncology |access-date=13 May 2022 |date=February 2022}}</ref> Since the 1980s, the incidence of colorectal cancer decreased, dropping by about 2% annually from 2014 to 2018 in adults aged 50 and older, due mainly to improved screening.<ref name=asco/> However, incidence of colorectal cancer has increased in individuals aged 25 to 50. In early 2023, the American Cancer Society (ACS) reported that 20% of diagnoses (of colon cancer) in 2019 were in patients under age 55, which is about double the rate in 1995, and rates of advanced disease increased by about 3% annually in people younger than 50. It predicted that, in 2023, an estimated 19,550 diagnoses and 3,750 deaths would be in people younger than 50.<ref>{{cite web | vauthors = Katella K |title=Colorectal Cancer: What Millennials and Gen Zers Need to Know |url=https://www.yalemedicine.org/news/colorectal-cancer-in-young-people |website=YaleMedicine}}</ref> Colorectal cancer also disproportionately affects the Black community, where the rates are the highest of any racial/ethnic group in the US. African Americans are about 20% more likely to get colorectal cancer and about 40% more likely to die from it than most other groups. Black Americans often experience greater obstacles to cancer prevention, detection, treatment, and survival, including systemic racial disparities that are complex and go beyond the obvious connection to cancer.

===United Kingdom===
In the UK about 41,000 people a year get colon cancer making it the fourth most common type.<ref>{{cite web|title=Bowel cancer {{!}} About bowel cancer {{!}} Cancer Research UK|url=http://www.cancerresearchuk.org/about-cancer/bowel-cancer/about-bowel-cancer|website=www.cancerresearchuk.org|access-date=12 May 2017|language=en|url-status=live|archive-url=https://web.archive.org/web/20170309175647/http://www.cancerresearchuk.org/about-cancer/bowel-cancer/about-bowel-cancer|archive-date=March 9, 2017|df=mdy-all}}</ref>

=== Australia ===
One in 19 men and one in 28 women in Australia will develop colorectal cancer before the age of 75; one in 10 men and one in 15 women will develop it by 85 years of age.<ref>{{Cite book|title=Cancer in Australia: an Overview, 2014. Cancer series No 90. Cat. No. CAN 88.|publisher=Australian Institute of Health and Welfare|year=2014|isbn=978-1-74249-677-1|location=Canberra}}</ref>

=== Papua New Guinea ===
In  [[Papua New Guinea]] and other Pacific Island States including the [[Solomon Islands]], colorectal cancer is a very rare cancer compared to lung, stomach, liver or breast cancer. It is estimated that 8 in 100,000 people are likely to develop colorectal cancer every year, while 24 in 100,000 women are likely to develop breast cancer.<ref>{{Cite book|title=Cancer in Papua New Guinea: an Overview, 2016. Cancer series No. 176. Cat. No. CAN 88. |publisher=Papua New Guinea Department of Health|year= 2016}}</ref>

== Early-onset colorectal cancer (EOCC) ==
A diagnosis of colorectal cancer in patients under 50 years of age is referred to as early-onset colorectal cancer (EOCC).<ref name="auto"/><ref name="Puzzono-2021a">{{Cite journal |last1=Puzzono |first1=Marta |last2=Mannucci |first2=Alessandro |last3=Grannò |first3=Simone |last4=Zuppardo |first4=Raffaella Alessia |last5=Galli |first5=Andrea |last6=Danese |first6=Silvio |last7=Cavestro |first7=Giulia Martina |date=2021 |title=The Role of Diet and Lifestyle in Early-Onset Colorectal Cancer: A Systematic Review |journal=Cancers |language=en |volume=13 |issue=23 |pages=5933 |doi=10.3390/cancers13235933 |doi-access=free |issn=2072-6694 |pmc=8657307 |pmid=34885046}}</ref> Instances of EOCC have increased over the last decade, specifically in patient populations aged 20 to 40 years old throughout North America, Europe, Australia, and China.<ref name="Puzzono-2021a" /><ref name="Vuik-2019">{{Cite journal |last1=Vuik |first1=Fanny ER |last2=Nieuwenburg |first2=Stella AV |last3=Bardou |first3=Marc |last4=Lansdorp-Vogelaar |first4=Iris |last5=Dinis-Ribeiro |first5=Mário |last6=Bento |first6=Maria J |last7=Zadnik |first7=Vesna |last8=Pellisé |first8=María |last9=Esteban |first9=Laura |last10=Kaminski |first10=Michal F |last11=Suchanek |first11=Stepan |last12=Ngo |first12=Ondřej |last13=Májek |first13=Ondřej |last14=Leja |first14=Marcis |last15=Kuipers |first15=Ernst J |date=2019 |title=Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years |journal=Gut |language=en |volume=68 |issue=10 |pages=1820–1826 |doi=10.1136/gutjnl-2018-317592 |issn=0017-5749 |pmc=6839794 |pmid=31097539}}</ref>

=== Incidence by age ===
The incidence of colorectal cancer in younger populations has increased over the last decade.<ref name="auto"/><ref name="Puzzono-2021a"/><ref name="Vuik-2019"/>  While advancements in diagnostic procedure may have some impact, reduced likelihood of screening among these populations suggests detection bias is not a major contributor to this trend.  It is more likely that cohort effects are contributing.<ref name="Vuik-2019" />

The population experiencing the greatest rise in EOCC cases are men and women aged 20 to 29 years old, with incidence increasing by 7.9% per year between 2004 and 2016.<ref name="Vuik-2019" /> Similarly, though less severe, men and women aged 30 to 39 experienced an increase in cases at a rate of 3.4% per year during that same time period. Despite these increases, the mortality rate for colorectal cancer has remained the same.<ref name="Vuik-2019" />

=== Risk factors ===
Risk factors associated with EOCC are akin to those of all colorectal cancer cases.<ref name="Puzzono-2021a"/> Observed cohort-effects are likely the product of generational shifts in lifestyle and environmental factors.<ref name="auto"/><ref name="Puzzono-2021a" />

=== Preventative screening ===
In 2018, the American Cancer Society modified their previous screening guideline for colorectal cancer from age 50 down to age 45 following the recognition of increasing cases of EOCC.<ref name="Vuik-2019"/> Individuals under the age of 60 have been identified as most susceptible to non-participation in colorectal cancer screening.<ref>{{Cite journal |last1=Unanue-Arza |first1=Saloa |last2=Solís-Ibinagagoitia |first2=Maite |last3=Díaz-Seoane |first3=Marta |last4=Mosquera-Metcalfe |first4=Isabel |last5=Idigoras |first5=Isabel |last6=Bilbao |first6=Isabel |last7=Portillo |first7=Isabel |date=2020-12-12 |title=Inequalities and risk factors related to non-participation in colorectal cancer screening programmes: a systematic review |journal=The European Journal of Public Health |volume=31 |issue=2 |pages=346–355 |doi=10.1093/eurpub/ckaa203 |issn=1101-1262 |pmc=8071594 |pmid=33313657}}</ref>

==History==
{{expand section|date=January 2024}}
Rectal cancer has been diagnosed in an Ancient Egyptian [[mummy]] who had lived in the [[Dakhleh Oasis]] during the [[Ptolemaic period]].<ref>{{cite journal | vauthors = Rehemtulla A | title = Dinosaurs and ancient civilizations: reflections on the treatment of cancer | journal = Neoplasia | volume = 12 | issue = 12 | pages = 957–968 | date = December 2010 | pmid = 21170260 | pmc = 3003131 | doi = 10.1593/neo.101588 }}</ref>

==Society and culture==
{{main|List of people diagnosed with colorectal cancer}}
In the United States, March is [[National Colon Cancer Awareness Month|colorectal cancer awareness month]].<ref name="Screen11">{{cite journal | vauthors = He J, Efron JE | title = Screening for colorectal cancer | journal = Advances in Surgery | volume = 45 | pages = 31–44 | year = 2011 | pmid = 21954677 | doi = 10.1016/j.yasu.2011.03.006 | hdl = 2328/11906 }}</ref>

==Research==
{{update section|reason=all sources > 5 years|date=January 2024}}
Preliminary [[in-vitro]] evidence suggests [[lactic acid bacteria]] (e.g., [[lactobacilli]], [[streptococci]] or [[lactococci]]) may be protective against the development and progression of colorectal cancer through several mechanisms such as [[antioxidant]] activity, [[Immunotherapy|immunomodulation]], promoting [[apoptosis|programmed cell death]], [[cytostasis|antiproliferative effects]], and [[epigenetic]] modification of cancer cells.<ref name="Zhong2014">{{cite journal | vauthors = Zhong L, Zhang X, Covasa M | title = Emerging roles of lactic acid bacteria in protection against colorectal cancer | journal = World Journal of Gastroenterology | volume = 20 | issue = 24 | pages = 7878–7886 | date = June 2014 | pmid = 24976724 | pmc = 4069315 | doi = 10.3748/wjg.v20.i24.7878 | doi-access = free }}</ref>

* [[The Cancer Genome Atlas]]<ref name="Muzny-2012"/>
* The Colorectal Cancer Atlas integrating genomic and proteomic data pertaining to colorectal cancer tissues and cell lines have been developed.<ref>{{cite web|url=http://colonatlas.org|title=Colorectal Cancer Atlas|url-status=live|archive-url=https://web.archive.org/web/20160113221047/http://www.colonatlas.org/|archive-date=January 13, 2016|df=mdy-all}}</ref>

==See also==
* [[Adenoma-carcinoma sequence]]

== References ==
{{Reflist|colwidth=30em}}

== External links ==
{{Medical condition classification and resources
| DiseasesDB = 2975
| ICD10 = {{ICD10|C|18||c|15}}, {{ICD10|C19}}, {{ICD10|C|20||c|15}}
| ICD9 = {{ICD9|153.0}}-{{ICD9|154.1}}
| OMIM = 114500
| OMIM_mult =
| MedlinePlus = 000262
| Name = Colorectal cancer
| ICDO = {{ICDO|8140|3}} (95% of cases)
| eMedicineSubj = med
| eMedicineTopic = 413
| eMedicine_mult = {{EMedicine2|med|1994}} {{EMedicine2|ped|3037}}
}}
{{Commons category}}
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* [https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer WHO fact sheet on colorectal cancer]

{{Gastroenterology}}
{{Digestive system neoplasia}}

{{Portal bar|Biology|Medicine}}
{{Authority control}}

{{DEFAULTSORT:Colorectal Cancer}}
[[Category:Colorectal cancer| ]]
[[Category:Conditions diagnosed by stool test]]
[[Category:Infectious causes of cancer]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Rectal diseases]]