The measurement of biochemical parameters in epidemiologic studies can contribute to a better und... more The measurement of biochemical parameters in epidemiologic studies can contribute to a better understanding of mechanisms of chemical carcinogenesis. Through identification and quantitation of chemicals in tissues or body fluids or through markers of « effective dose » such as DNA adducts, mechanisms of cancer etiology and pathogenesis can be elucidated. Different approaches and the associated methodologic problems are discussed along with examples. As a comprehensive case study, the relationship between aromatic amine exposure and bladder cancer is considered in light of different biochemical aspects which could be the target of epidemiologic studies.
A novel line of research suggests that eating at nighttime may have several metabolic consequence... more A novel line of research suggests that eating at nighttime may have several metabolic consequences that are highly relevant to breast cancer. We investigated the association between nighttime eating habits after 10 p.m. and breast cancer in Hong Kong women. A hospital-based case-control study was conducted during 2012-2015. A total of 922 patients with incident breast cancer (cases) and 913 hospital controls were recruited and interviewed using a standard questionnaire including information on eating behavior during both daytime and nighttime. We collected the timing, duration, types and frequencies of food intake of eating at nighttime. Odds ratios (ORs) for the risk of breast cancer in relation to nighttime eating-related variables were calculated by unconditional multivariable logistic regression. Eating at night after 10 pm was significantly associated with breast cancer with an adjusted OR of 1.50 (95% confidence interval (CI) 1.06-2.12, P = 0.02), and the associations were str...
Analyse des differents criteres traditionnels servant a identifier et categoriser les utilisateur... more Analyse des differents criteres traditionnels servant a identifier et categoriser les utilisateurs de systemes de comunication, qui s'inscrit dans une etude plus large sur les difficultes et les potentialites liees a la conception des systemes de communication
International journal of epidemiology, Jan 16, 2015
Coffee drinkers had a higher risk of lung cancer in some previous studies, but as heavy coffee dr... more Coffee drinkers had a higher risk of lung cancer in some previous studies, but as heavy coffee drinkers tend to also be cigarette smokers, such findings could be confounded. Therefore, we examined this association in the nearly half a million participants of the US NIH-AARP Diet and Health Study. Typical coffee intake and smoking history were queried at baseline. During 4 155 256 person-years of follow-up, more than 9000 incident lung cancer cases occurred. We used Cox proportional hazards regression to estimate hazard ratios (HRs)and 95% confidence intervals for coffee intake and subsequent incidence of lung cancer. We also comprehensively adjusted for tobacco smoking and examined associations by detailed strata of tobacco use. Coffee drinkers were far more likely to smoke than non-drinkers. Although coffee drinking was associated with lung cancer in age- and sex- adjusted models (HR for ≥ 6 cups/day compared with none: 4.56, 4.08-5.10), this association was substantially attenuate...
Juvenile myelomonocytic leukemia (JMML) is a pediatric myeloproliferative neoplasm that arises fr... more Juvenile myelomonocytic leukemia (JMML) is a pediatric myeloproliferative neoplasm that arises from malignant transformation of the stem cell compartment and results in increased production of myeloid cells. Somatic and germline variants in CBL (Casitas B-lineage lymphoma proto-oncogene) have been associated with JMML. We report an incompletely penetrant CBL Y371C mutation discovered by whole-exome sequencing in three individuals with JMML in a large pedigree with 35 years of follow-up. The Y371 residue is highly evolutionarily conserved among CBL orthologs and paralogs. In silico bioinformatics prediction programs suggested that the Y371C mutation is highly deleterious. Protein structural modeling revealed that the Y371C mutation abrogated the ability of the CBL protein to adopt a conformation that is required for ubiquitination. Clinically, the three mutation-positive JMML individuals exhibited variable clinical courses; in two out of three, primary hematologic abnormalities persisted into adulthood with minimal clinical symptoms. The penetrance of the CBL Y371C mutation was 30 % for JMML and 40 % for all leukemia. Of the 8 mutation carriers in the family with available photographs, only one had significant dysmorphic features; we found no evidence of a clinical phenotype consistent with a "CBL syndrome". Although CBL Y371C has been previously reported in familial JMML, we are the first group to follow a complete pedigree harboring this mutation for an extended period, revealing additional information about this variant's penetrance, function and natural history.
Eighty-four healthy Chinese male control subjects derived from an occupation-based case-control s... more Eighty-four healthy Chinese male control subjects derived from an occupation-based case-control study of bladder cancer were evaluated for hepatic N-acetyltransferase activity by dapsone and for NAT2 genotype using allele-specific amplification of peripheral leukocyte DNA by the polymerase chain reaction. Fifty-nine percent of the overall variation in acetylation activity was explained by genotype (p < 0.0001). The remaining variation in acetylation was not associated with dapsone N-hydroxylation activity, age, current smoking status, or weight in the study population, or within any genotype subgroup. Although acetylation activity in the homozygous mutant group did not overlap with the other genotype categories, there was moderate overlap in acetylation between the heterozygous mutant and wildtype groups, and substantial variation in acetylation within them. Considering all subjects with the identical NAT2 genotype as phenotypically similar and all subjects with differing NAT2 genotypes as phenotypically distinct may result in misclassification of metabolic risk factors in epidemiological investigations. As such, it would seem prudent, where possible, to collect both acetylation phenotype and NAT2 genotype data, since the advantages and limitations of these two sources of information complement, and serve to assess the accuracy of each other.
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2014
The advent of low-dose helical computed tomography for lung cancer screening will likely lead to ... more The advent of low-dose helical computed tomography for lung cancer screening will likely lead to an increase in the detection of stage I lung cancer. Presently, these patients are primarily treated with surgery alone and approximately 30% will develop recurrence and die. Biomarkers that can identify patients for whom adjuvant chemotherapy would be a benefit could significantly reduce both patient morbidity and mortality. Herein, we sought to build a prognostic inflammatory-based classifier for stage I lung cancer. We performed a retrospective analysis of 548 European American lung cancer cases prospectively enrolled in the Prostate, Lung, Colorectal and Ovarian study. C-reactive protein, interleukin (IL)-6, IL-8, tumor necrosis factor-α, and IL-1β were measured using an ultrasensitive electrochemiluminescence immunoassay in serum samples collected at the time of study entry. IL-6 and IL-8 were each associated with significantly shorter survival (hazard ratio [HR], 1.33; 95% confiden...
Targeting smokers at higher lung cancer risk can improve efficiency and reduce false-positive det... more Targeting smokers at higher lung cancer risk can improve efficiency and reduce false-positive detection in lung cancer screening. We evaluated whether time to first cigarette after waking (TTFC), a single-item measure of nicotine dependency, could improve stratification of lung cancer risk beyond standard smoking metrics (intensity, duration, and pack-years). In 3249 ever-smokers (n = 1812 case subjects; n = 1437 control subjects) from a population-based case-control study in Italy, we examined the association between TTFC and lung cancer using logistic regression and estimated lung cancer incidence by levels of TTFC, and intensity, duration, and pack-years using absolute risk regression. Significance tests were two-sided. Compared with smokers with TTFC greater than 60 minutes, the lung cancer odds ratios for TTFC of 31 to 60 minutes, 6 to 30 minutes, and 5 or fewer minutes (by increasing dependency) were 2.57 (95% confidence interval [CI] = 2.03 to 3.26), 2.27 (95% CI = 1.79 to 2....
A comprehensive characterization of the effects of cigarette smoke on systemic soluble immune/inf... more A comprehensive characterization of the effects of cigarette smoke on systemic soluble immune/inflammatory markers may provide insight into the mechanisms through which smoking causes disease. Levels of 78 inflammation, immune, and metabolic markers were measured using multiplex immune assays in 1819 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) participants aged 55 to 74 years from three existing nested case-control studies. These data were made representative of the entire PLCO screening arm through reweighting with weights estimated in logistic regression models. We assessed associations between smoking status, cigarettes smoked per day, and time since quitting with dichotomized marker levels using adjusted weighted logistic regression models. Current smoking was associated with 10 inflammation markers after correcting for multiple testing, encompassing several components of the immune/inflammation response. Levels of seven of these markers (interleukin [IL...
The measurement of biochemical parameters in epidemiologic studies can contribute to a better und... more The measurement of biochemical parameters in epidemiologic studies can contribute to a better understanding of mechanisms of chemical carcinogenesis. Through identification and quantitation of chemicals in tissues or body fluids or through markers of « effective dose » such as DNA adducts, mechanisms of cancer etiology and pathogenesis can be elucidated. Different approaches and the associated methodologic problems are discussed along with examples. As a comprehensive case study, the relationship between aromatic amine exposure and bladder cancer is considered in light of different biochemical aspects which could be the target of epidemiologic studies.
A novel line of research suggests that eating at nighttime may have several metabolic consequence... more A novel line of research suggests that eating at nighttime may have several metabolic consequences that are highly relevant to breast cancer. We investigated the association between nighttime eating habits after 10 p.m. and breast cancer in Hong Kong women. A hospital-based case-control study was conducted during 2012-2015. A total of 922 patients with incident breast cancer (cases) and 913 hospital controls were recruited and interviewed using a standard questionnaire including information on eating behavior during both daytime and nighttime. We collected the timing, duration, types and frequencies of food intake of eating at nighttime. Odds ratios (ORs) for the risk of breast cancer in relation to nighttime eating-related variables were calculated by unconditional multivariable logistic regression. Eating at night after 10 pm was significantly associated with breast cancer with an adjusted OR of 1.50 (95% confidence interval (CI) 1.06-2.12, P = 0.02), and the associations were str...
Analyse des differents criteres traditionnels servant a identifier et categoriser les utilisateur... more Analyse des differents criteres traditionnels servant a identifier et categoriser les utilisateurs de systemes de comunication, qui s'inscrit dans une etude plus large sur les difficultes et les potentialites liees a la conception des systemes de communication
International journal of epidemiology, Jan 16, 2015
Coffee drinkers had a higher risk of lung cancer in some previous studies, but as heavy coffee dr... more Coffee drinkers had a higher risk of lung cancer in some previous studies, but as heavy coffee drinkers tend to also be cigarette smokers, such findings could be confounded. Therefore, we examined this association in the nearly half a million participants of the US NIH-AARP Diet and Health Study. Typical coffee intake and smoking history were queried at baseline. During 4 155 256 person-years of follow-up, more than 9000 incident lung cancer cases occurred. We used Cox proportional hazards regression to estimate hazard ratios (HRs)and 95% confidence intervals for coffee intake and subsequent incidence of lung cancer. We also comprehensively adjusted for tobacco smoking and examined associations by detailed strata of tobacco use. Coffee drinkers were far more likely to smoke than non-drinkers. Although coffee drinking was associated with lung cancer in age- and sex- adjusted models (HR for ≥ 6 cups/day compared with none: 4.56, 4.08-5.10), this association was substantially attenuate...
Juvenile myelomonocytic leukemia (JMML) is a pediatric myeloproliferative neoplasm that arises fr... more Juvenile myelomonocytic leukemia (JMML) is a pediatric myeloproliferative neoplasm that arises from malignant transformation of the stem cell compartment and results in increased production of myeloid cells. Somatic and germline variants in CBL (Casitas B-lineage lymphoma proto-oncogene) have been associated with JMML. We report an incompletely penetrant CBL Y371C mutation discovered by whole-exome sequencing in three individuals with JMML in a large pedigree with 35 years of follow-up. The Y371 residue is highly evolutionarily conserved among CBL orthologs and paralogs. In silico bioinformatics prediction programs suggested that the Y371C mutation is highly deleterious. Protein structural modeling revealed that the Y371C mutation abrogated the ability of the CBL protein to adopt a conformation that is required for ubiquitination. Clinically, the three mutation-positive JMML individuals exhibited variable clinical courses; in two out of three, primary hematologic abnormalities persisted into adulthood with minimal clinical symptoms. The penetrance of the CBL Y371C mutation was 30 % for JMML and 40 % for all leukemia. Of the 8 mutation carriers in the family with available photographs, only one had significant dysmorphic features; we found no evidence of a clinical phenotype consistent with a "CBL syndrome". Although CBL Y371C has been previously reported in familial JMML, we are the first group to follow a complete pedigree harboring this mutation for an extended period, revealing additional information about this variant's penetrance, function and natural history.
Eighty-four healthy Chinese male control subjects derived from an occupation-based case-control s... more Eighty-four healthy Chinese male control subjects derived from an occupation-based case-control study of bladder cancer were evaluated for hepatic N-acetyltransferase activity by dapsone and for NAT2 genotype using allele-specific amplification of peripheral leukocyte DNA by the polymerase chain reaction. Fifty-nine percent of the overall variation in acetylation activity was explained by genotype (p < 0.0001). The remaining variation in acetylation was not associated with dapsone N-hydroxylation activity, age, current smoking status, or weight in the study population, or within any genotype subgroup. Although acetylation activity in the homozygous mutant group did not overlap with the other genotype categories, there was moderate overlap in acetylation between the heterozygous mutant and wildtype groups, and substantial variation in acetylation within them. Considering all subjects with the identical NAT2 genotype as phenotypically similar and all subjects with differing NAT2 genotypes as phenotypically distinct may result in misclassification of metabolic risk factors in epidemiological investigations. As such, it would seem prudent, where possible, to collect both acetylation phenotype and NAT2 genotype data, since the advantages and limitations of these two sources of information complement, and serve to assess the accuracy of each other.
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2014
The advent of low-dose helical computed tomography for lung cancer screening will likely lead to ... more The advent of low-dose helical computed tomography for lung cancer screening will likely lead to an increase in the detection of stage I lung cancer. Presently, these patients are primarily treated with surgery alone and approximately 30% will develop recurrence and die. Biomarkers that can identify patients for whom adjuvant chemotherapy would be a benefit could significantly reduce both patient morbidity and mortality. Herein, we sought to build a prognostic inflammatory-based classifier for stage I lung cancer. We performed a retrospective analysis of 548 European American lung cancer cases prospectively enrolled in the Prostate, Lung, Colorectal and Ovarian study. C-reactive protein, interleukin (IL)-6, IL-8, tumor necrosis factor-α, and IL-1β were measured using an ultrasensitive electrochemiluminescence immunoassay in serum samples collected at the time of study entry. IL-6 and IL-8 were each associated with significantly shorter survival (hazard ratio [HR], 1.33; 95% confiden...
Targeting smokers at higher lung cancer risk can improve efficiency and reduce false-positive det... more Targeting smokers at higher lung cancer risk can improve efficiency and reduce false-positive detection in lung cancer screening. We evaluated whether time to first cigarette after waking (TTFC), a single-item measure of nicotine dependency, could improve stratification of lung cancer risk beyond standard smoking metrics (intensity, duration, and pack-years). In 3249 ever-smokers (n = 1812 case subjects; n = 1437 control subjects) from a population-based case-control study in Italy, we examined the association between TTFC and lung cancer using logistic regression and estimated lung cancer incidence by levels of TTFC, and intensity, duration, and pack-years using absolute risk regression. Significance tests were two-sided. Compared with smokers with TTFC greater than 60 minutes, the lung cancer odds ratios for TTFC of 31 to 60 minutes, 6 to 30 minutes, and 5 or fewer minutes (by increasing dependency) were 2.57 (95% confidence interval [CI] = 2.03 to 3.26), 2.27 (95% CI = 1.79 to 2....
A comprehensive characterization of the effects of cigarette smoke on systemic soluble immune/inf... more A comprehensive characterization of the effects of cigarette smoke on systemic soluble immune/inflammatory markers may provide insight into the mechanisms through which smoking causes disease. Levels of 78 inflammation, immune, and metabolic markers were measured using multiplex immune assays in 1819 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) participants aged 55 to 74 years from three existing nested case-control studies. These data were made representative of the entire PLCO screening arm through reweighting with weights estimated in logistic regression models. We assessed associations between smoking status, cigarettes smoked per day, and time since quitting with dichotomized marker levels using adjusted weighted logistic regression models. Current smoking was associated with 10 inflammation markers after correcting for multiple testing, encompassing several components of the immune/inflammation response. Levels of seven of these markers (interleukin [IL...
Uploads
Papers by Neil Caporaso