Canadian Population-based Case-control Study Research Articles

Ambient polycyclic aromatic hydrocarbon exposure and breast cancer risk in a population-based Canadian case–control study

PurposePolycyclic aromatic hydrocarbons (PAHs) represent a class of ubiquitous pollutants recognized as established human carcinogens and endocrine-disrupting chemicals. PAHs have seldom been modeled at the population-level in epidemiological studies. Fluoranthene is a prevalent PAH in urban settings and correlates with the occurrence of other PAHs. The purpose of this study was to evaluate associations between long-term residential exposure to ambient PAHs and breast cancer risk, both pre- and post-menopausal, in Canada.MethodsUsing the National Enhanced Cancer Surveillance System (NECSS), a national-scale Canadian population-based case–control study, annual fluoranthene exposures were estimated using the GEM-MACH-PAH chemical transport model on the basis of geocoded residential histories throughout a 20-year exposure window. Odds ratios (ORs) and 95% confidence intervals (CIs) controlling for potential confounders were estimated using logistic regression. Separate analyses were conducted for Ontario and national samples given a finer-resolution exposure surface and additional risk factor information available for Ontario.ResultsPositive associations were observed between fluoranthene exposure and premenopausal breast cancer, with inconsistent findings for postmenopausal breast cancer. For premenopausal breast cancer, adjusted ORs of 2.48 (95% CI: 1.29, 4.77) and 1.59 (95% CI: 1.11, 2.29) were observed when comparing the second highest category of exposure to the lowest, among the Ontario and national samples, respectively. For postmenopausal breast cancer, adjusted ORs were 1.10 (95% CI: 0.67, 1.80) and 1.33 (95% CI: 1.02, 1.73). Associations for the highest level of exposure, across both samples and menopausal strata, were non-significant.ConclusionThis study provides support for the hypothesis that ambient PAH exposures increase the risk of premenopausal breast cancer.

Silica and asbestos exposure at work and the risk of bladder cancer in Canadian men: a population-based case-control study

BackgroundSilica and asbestos are recognized lung carcinogens. However, their role in carcinogenesis at other organs is less clear. Clearance of inhaled silica particles and asbestos fibers from the lungs may lead to translocation to sites such as the bladder where they may initiate carcinogenesis. We used data from a Canadian population-based case-control study to evaluate the associations between these workplace exposures and bladder cancer.MethodsData from a population-based case-control study were used to characterize associations between workplace exposure to silica and asbestos and bladder cancer among men. Bladder cancer cases (N = 658) and age-frequency matched controls (N = 1360) were recruited within the National Enhanced Cancer Surveillance System from eight Canadian provinces (1994–97). Exposure concentration, frequency and reliability for silica and asbestos were assigned to each job, based on lifetime occupational histories, using a combination of job-exposure profiles and expert review. Exposure was modeled as ever/never, highest attained concentration, duration (years), highest attained frequency (% worktime) and cumulative exposure. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated using adjusted logistic regression.ResultsA modest (approximately 20%) increase in bladder cancer risk was found for ever having been exposed to silica, highest attained concentration and frequency of exposure but this increase was not statistically significant. Relative to unexposed, the odds of bladder cancer were 1.41 (95%CI: 1.01–1.98) times higher among men exposed to silica at work for ≥27 years. For asbestos, relative to unexposed, an increased risk of bladder cancer was observed for those first exposed ≥20 years ago (OR:2.04, 95%CI:1.25–3.34), those with a frequency of exposure of 5–30% of worktime (OR:1.45, 95%CI:1.06–1.98), and for those with < 10 years of exposure at low concentrations (OR:1.75, 95%CI:1.10–2.77) and the lower tertile of cumulative exposure (OR:1.69, 95%CI:1.07–2.65). However, no clear exposure-response relationships emerged.ConclusionsOur results indicate a slight increase in risk of bladder cancer with exposure to silica and asbestos, suggesting that the effects of these agents are broader than currently recognized. The findings from this study inform evidence-based action to enhance cancer prevention efforts, particularly for workers in industries with regular exposure.

Occupational Exposure to Diesel and Gasoline Engine Exhausts and the Risk of Kidney Cancer in Canadian Men.

IntroductionKidney cancer is the fifth most common incident cancer in Canadian men. Diesel and gasoline exhausts are common workplace exposures that have been examined as risk factors for non-lung cancer sites, including the kidney, but limitations in exposure assessment methods have contributed to inconsistent findings. The objective of this study was to assess the relationship between occupational gasoline and diesel engine exhausts and the risk of kidney cancer in men.MethodsThe National Enhanced Cancer Surveillance System (NECSS) is a Canadian population-based case–control study conducted in 1994–1997. Incident kidney cancer cases were identified using provincial registries, while the control series was identified through random-digit dialing, or provincial administrative databases. Self-reported questionnaires were used to obtain information on lifetime occupational history and cancer risk factors. Two hygienists, blinded to case status, coded occupational histories for diesel and gasoline exhaust exposures using concentration, frequency, duration, and reliability. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) separately by exhaust type. The separate and combined impacts of both engine exhausts were also examined. ORs were adjusted for age, province, body mass index, occupational secondhand smoke exposure, and education.ResultsOf the kidney cancer cases (n = 712), 372 (52%) had exposure to both exhausts at some point, and 984 (40%) of the controls (n = 2457) were ever exposed. Workers who had ever been exposed to engine exhausts were more likely to have kidney cancer than those who were never exposed (OR diesel = 1.23, 95% CI = 0.99–1.53; OR gasoline = 1.51, 95% CI = 1.23–1.86). Exposure to gasoline exhaust was consistently associated with kidney cancer in a dose–response manner (P value for trends in highest attained and cumulative exposure both <0.0001). Those men with high cumulative exposure to both gasoline and diesel exhaust had a 76% increased odds of kidney cancer (95% CI = 1.27–2.43).ConclusionsThis study provides evidence that occupational gasoline, and to a lesser extent, diesel exhaust exposure may increase the risk of kidney cancer.

Combined oral contraceptive use before the first birth and epithelial ovarian cancer risk

Background:Combined oral contraceptive (COC) use reduces epithelial ovarian cancer (EOC) risk. However, little is known about risk with COC use before the first full-term pregnancy (FFTP).Methods:This Canadian population-based case–control study (2001–2012) included 854 invasive cases/2139 controls aged ⩾40 years who were parous and had information on COC use. We estimated odds ratios (aORs) and 95% confidence intervals (CI) adjusted for study site, age, parity, breastfeeding, age at FFTP, familial breast/ovarian cancer, tubal ligation, and body mass.Results:Among parous women, per year of COC use exclusively before the FFTP was associated with a 9% risk reduction (95% CI=0.86–0.96). Results were similar for high-grade serous and endometrioid/clear cell EOC. In contrast, per year of use exclusively after the FFTP was not associated with risk (aOR=0.98, 95% CI=0.95–1.02).Conclusions:Combined oral contraceptive use before the FFTP may provide a risk reduction that remains for many years, informing possible prevention strategies.

Exposure to ambient air pollution in Canada and the risk of adult leukemia

There is a paucity of studies investigating adult leukemia and air pollution. To address this gap, we analyzed data from a Canadian population-based case–control study conducted in 1994–1997. Cases were 1064 adults with incident leukemia and controls were 5039 healthy adults. We used data from satellites and fixed-site monitoring stations to estimate residential concentrations of NO2 and fine particulate matter (PM2.5) for the period prior to diagnosis, starting in 1975 and ending in 1994. We modeled the average annual exposure of each subject. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated using logistic regression, adjusted for age, gender, province, smoking, education, body mass index, income, and self-reported exposures to ionizing radiation and benzene. We found an ‘n-shaped’ response function between exposure to NO2 and all forms of leukemia: from the tenth percentile to the median (4.51 to 14.66ppb), the OR was 1.20; 95% CI: 0.97–1.48 and from the 75th percentile to the 90th (22.75 to 29.7ppb), the OR was 0.79; 95% CI 0.68–0.93. For PM2.5 we found a response function consistent with a linear model, with an OR per 10μg/m3 of 0.97 (95% CI 0.75–1.26). For chronic lymphocytic leukemia we found response functions that were consistent with a simple linear model, with an OR per 5ppb of NO2 of 0.93 (95% CI 0.86–1.00) and an OR per 10μg/m3 of PM2.5 of 0.62 (95% CI 0.42–0.93). In summary, for chronic lymphocytic leukemia we found no evidence of an association with air pollution and with all forms of leukemia we found weak evidence of an association only at low concentrations of NO2. It is possible that these inconsistent results may have arisen because of unaccounted urban/rural differences or possibly from a selection effect, especially among controls.

Occupational Exposure to Diesel and Gasoline Engine Emissions and Bladder Cancer Risk in Men: a Canadian Population-Based Case-Control Study

Background: The International Agency for Research on Cancer has classified diesel exhaust as a carcinogen and gasoline exhaust as a possible carcinogen based on evidence for lung cancer. Our goal was to determine whether a positive association exists between occupational exposure to diesel or gasoline exhaust and bladder cancer. Methods: A population-based design was used to recruit 670 cases and 2547 frequency-matched controls from eight Canadian provinces between 1994 and 1997. Lifetime occupational history, including job title, status and duties, and information on possible risk factors was obtained by self-reported questionnaire. Concentration and frequency of occupational exposure to diesel and gasoline exhaust, and a measure of the reliability of exposure assessment, was assigned for each job using a job-exposure matrix supplemented by expert review. Exposure metrics were modeled as ever-never, highest attained concentration, duration, and cumulative exposure. Unconditional logistic regression was used to calculate odds ratios and their 95% confidence intervals. Analyses were restricted to estimates with high reliability and adjustment was made for proxy respondent, province, age, smoking, alcohol, occupational silica and aromatic amine exposure. Results: Relative to unexposed men, elevated odds of bladder cancer were observed for men whose highest attained diesel exhaust exposure concentration was high (1.97, 1.08-3.58) and who spent more than 30% of time at work exposed to diesel (1.80, 1.02-3.15). A statistically significant trend in increased risk of bladder cancer was observed with increasing duration of exposure to medium/high concentrations of diesel exhaust (&gt;20 years, 1.82, 1.07-3.10, p-trend=0.002). We found no association between exposure to gasoline exhaust and bladder cancer. Conclusions: Our results suggest that occupational exposure to diesel exhaust increases bladder cancer risk in men, independent of smoking and other occupational exposures.

Long-term Residential Exposure to Air Pollution and Lung Cancer Risk

There is accumulating evidence that air pollution causes lung cancer. Still, questions remain about exposure misclassification, the components of air pollution responsible, and the histological subtypes of lung cancer that might be produced. We investigated lung cancer incidence in relation to long-term exposure to three ambient air pollutants and proximity to major roads, using a Canadian population-based case-control study. We compared 2,390 incident, histologically confirmed lung cancer cases with 3,507 population controls in eight Canadian provinces from 1994 to 1997. We developed spatiotemporal models for the whole country to estimate annual residential exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) over a 20-year exposure period. We carried out a subanalysis in urban centers, using exposures derived from fixed-site air pollution monitors, and also examined traffic proximity measures. Hierarchical logistic regression models incorporated a comprehensive set of individual and geographic covariates. The increase in lung cancer incidence (expressed as fully adjusted odds ratios [ORs]) was 1.29 (95% confidence interval = 0.95-1.76) with a ten-unit increase in PM2.5 (μg/m), 1.11 (1.00-1.24) with a ten-unit increase in NO2 (ppb), and 1.09 (0.85-1.39) with a ten-unit increase in O3 (ppb). The urban monitor-based subanalyses generally supported the national results, with larger associations for NO2 (OR = 1.34; 1.07-1.69) per 10 ppb increase. No dose-response trends were observed, and no clear relationships were found for specific histological cancer subtypes. There was the suggestion of increased risk among those living within 100 m of highways, but not among those living near major roads. Lung cancer incidence in this Canadian study was increased most strongly with NO2 and PM2.5 exposure. Further investigation is needed into possible effects of O3 on development of lung cancer.

Body mass index, lifetime smoking intensity and lung cancer risk

There is as yet no generally accepted explanation for the common finding that low body mass index (BMI) is associated with an increased risk of lung cancer. We investigated this association in a Canadian population-based case-control study (1996-2002) with a particular view to assessing the hypothesis that the observed association was due to residual confounding by smoking. Analyses were based on 1,076 cases and 1,439 controls who provided their height at enrollment and their weight at two points in time, at age 20 and 2 years before enrollment. BMI, in kg/m(2) , was classified into underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9), and obese (≥30). Smoking history was synthesized into a comprehensive smoking index (CSI) that integrated duration, intensity and time since quitting. Odds ratios (ORs) and 95% confidence intervals (CIs) for BMI-lung cancer associations were estimated, adjusting for CSI as well as several sociodemographic, lifestyle and occupational factors. The normal BMI category was used as the reference. Among those who were underweight at age 20, there was a lower risk of lung cancer (OR = 0.69, 95% CI: 0.50-0.95). Conversely, lung cancer risk was increased among those who were underweight 2 years before enrollment (OR = 2.30, 95% CI: 1.30-4.10). The results were almost identical when stratifying analyses based on smoking history into never/lighter and heavier smokers. The inverse association between recent BMI and lung cancer is unlikely to be largely attributable to residual confounding by smoking. Reverse causality or a true relationship between BMI and lung cancer remain plausible.

Soft-Tissue Sarcoma and Pesticides Exposure in Men

The objective was to investigate the putative associations of specific pesticides with soft-tissue sarcoma (STS). A Canadian population-based case-control study conducted in six provinces was used in this analysis. The study design consisted of two stages: a self-administered postal questionnaire and a telephone interview for those reporting pesticides exposure of 10 hours per year or more; and a 15% random sample of the remainder. Conditional logistic regression was used to fit the statistical models. A positive history of cancer among first-degree relatives and exposure to aldrin and diazinon were statistically significant independent predictors of an increased risk for STS, whereas diagnosis of whopping cough lowered the risk of STS. The incidence of STS was associated with specific insecticides after adjustment for other independent predictors.

Association between frequency and intensity of recreational physical activity and epithelial ovarian cancer risk by age period

The objective of this study was to examine the association between recreational physical activity across the life span and epithelial ovarian cancer. This relationship was investigated using data from the Ontario arm of the National Enhanced Cancer Surveillance Study, a Canadian population-based case-control study. Data were collected from 240 epithelial ovarian cases and 891 female controls using a self-administered questionnaire. The frequency and intensity of recreational activity in four age periods (mid-teens, early 30s, early 50s, 2 years ago) were examined. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression. Participation up to two times/week, but not more than two times/week, in strenuous recreational activity in mid-teens (OR = 1.69, 95% CI=1.15-2.49) and early 30s (OR = 1.45, 95% CI=1.03-2.05) was associated with increased risk of ovarian cancer. For activity 2 years ago, participation in both strenuous activity (OR = 0.69, 95% CI=0.47-1.01) and moderate activity (OR = 0.55, 95% CI=0.34-0.88) up to two times/week was associated with reduced ovarian cancer risk. Participating more than two times/week was not associated with ovarian cancer risk. Strenuous activity performed in early 50s and moderate activity performed in mid-teens, early 30s, and early 50s were unrelated to risk. In conclusion, strenuous recreational activity early in life may increase the risk of ovarian cancer, whereas more recent recreational activity may reduce the risk.

Timing in Collection of Stool Samples

We read with great interest the Report “Diversity of the human intestinal microbial flora” by P. B. Eckburg et al. (10 June, p. [1635][1]; published online 14 Apr.). We applaud the authors for advancing this important field by undertaking comprehensive 16S rDNA sequencing to describe the composition of the microbiota in stools and at six sites of the colon in each of three human volunteers. The analyzed 13,355 prokaryotic ribosomal RNA gene sequences represent the largest 16S rDNA microflora data set reported to date in any species. On the basis of their analysis, the authors suggest that “differences between stool and mucosa community composition” exist. We question the validity of this conclusion, based on our own observation that stool microflora composition can vary significantly in stool samples collected before and after a colonoscopy ([1][2]). The authors compare microflora composition in colon biopsy samples obtained during colonoscopy with a stool sample collected a month afterwards. The authors acknowledge potential problems with their interpretation because of the delayed stool collection, but a rationale for collecting delayed stool samples is not given. This Report has significantly expanded our knowledge of the diversity of the intestinal microflora in a few subjects. However, if we ever want to correlate microflora composition with health or disease, we will have to design studies aimed at understanding the variation in the microflora composition in a large cohort of human subjects. 1. 1.[↵][3]1. V. Mai, 2. O. C. Stine, 3. J. G. Morris Jr. , unpublished data. # Response {#article-title-2} Our large-scale comparative analysis of bacterial and archaeal 16S rDNA sequences in the colon and stool revealed significant intersubject variability and patchy heterogeneity among the colonic mucosal bacterial populations. Regarding the statistical differences we reported between stool and adherent mucosal populations, subjects B and C harbored different bacterial populations in their colonic mucosa compared with their stool samples collected 4 weeks later, while the mucosal populations in subject A were subsets of the population observed in stool collected 4 weeks after colonoscopy. Each subject's stool community was more similar to the communities of their own mucosal samples than to any community from a different subject. We acknowledged that the statistically significant difference between the bacterial composition of the stool and colonic mucosa may have been due to the 4-week delay in stool collection after colonoscopy. The collection of stool was not originally planned in the large Canadian population-based case control study from which the control subjects were selected. For this study of three healthy subjects, from whom the colonic tissue biopsies had already been collected, we chose to obtain stool samples 1 month after colonoscopy when each subject had full recovery of stable, baseline bowel function. Despite the original study design, we agree with Mai et al. that stool samples before endoscopy may provide more reliable representations of the steady-state stool bacterial population. However, a controlled comparative study is needed to reveal the degree to which stools are microbiologically dissimilar at various time intervals before and after bowel cleansing. A small study using denaturing gradient gel electrophoresis has suggested that the bacterial composition in colonic mucosal biopsies differs significantly from that in stool collected prior to the procedure ([1][4]), supporting our conclusions that significant differences exist between these microbial communities. Future studies should address these issues with high-resolution molecular methods and a greater number of subjects. 1. 1.[↵][5]1. E. G. Zoetendal 2. et al. , Appl. Environ. Microbiol. 68, 3401 (2002). [OpenUrl][6][Abstract/FREE Full Text][7] [1]: /lookup/doi/10.1126/science.1110591 [2]: #ref-1 [3]: #xref-ref-1-1 View reference 1. in text [4]: #ref-2 [5]: #xref-ref-2-1 View reference 1. in text [6]: {openurl}?query=rft.jtitle%253DApplied%2Band%2BEnvironmental%2BMicrobiology%26rft.stitle%253DAppl.%2BEnviron.%2BMicrobiol.%26rft.aulast%253DZoetendal%26rft.auinit1%253DE.%2BG.%26rft.volume%253D68%26rft.issue%253D7%26rft.spage%253D3401%26rft.epage%253D3407%26rft.atitle%253DMucosa-Associated%2BBacteria%2Bin%2Bthe%2BHuman%2BGastrointestinal%2BTract%2BAre%2BUniformly%2BDistributed%2Balong%2Bthe%2BColon%2Band%2BDiffer%2Bfrom%2Bthe%2BCommunity%2BRecovered%2Bfrom%2BFeces%26rft_id%253Dinfo%253Adoi%252F10.1128%252FAEM.68.7.3401-3407.2002%26rft_id%253Dinfo%253Apmid%252F12089021%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [7]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYWVtIjtzOjU6InJlc2lkIjtzOjk6IjY4LzcvMzQwMSI7czo0OiJhdG9tIjtzOjIzOiIvc2NpLzMxMC81NzUxLzExMTguYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9

Antidepressant medication use and non-Hodgkin's lymphoma risk: no association.

Animal and human studies have suggested that antidepressant medications may be associated with several cancers. The authors evaluated the association between antidepressant medication use and the risk of non-Hodgkin's lymphoma using a Canadian population-based case-control study, the National Enhanced Cancer Surveillance Study. Non-Hodgkin's lymphoma cases (n=638) diagnosed in 1995-1996 were identified using the Ontario Cancer Registry, and controls (n=1,930) were identified from the Ontario Ministry of Finance Property Assessment Database. Antidepressant medication use was ascertained using a self-administered questionnaire. Multivariate logistic regression was used to estimate odds ratios. "Ever" use of antidepressant medications was not associated with non-Hodgkin's lymphoma risk. The odds ratio for non-Hodgkin's lymphoma with 25 or more months of tricyclic antidepressant medication use was 1.6; however, this was nonsignificant. Duration or history of use or individual types of antidepressant medications were not associated with non-Hodgkin's lymphoma risk. These findings do not support an increased risk of non-Hodgkin's lymphoma with antidepressant medication use.

Environmental tobacco smoke and the risk of pancreatic cancer: findings from a Canadian population-based case-control study.

Despite the fact that tobacco is a well-recognized risk factor for pancreatic cancer, no study has yet reported on the association between environmental tobacco smoke (ETS) and this malignancy. We investigated the relationship between pancreatic cancer and childhood and adult exposure to ETS using a case-control study design. Our study population consisted of 583 pancreatic cancer cases and 4,813 population-based controls that were identified within 8 Canadian provinces between 1994 and 1997. Mail-out questionnaires were used to collect risk factor information and a lifetime residential and occupational history of exposure to ETS. Among never smokers, those who were exposed to ETS both as a child and as an adult had an odds ratio of 1.21 (95% CI=0.60-2.44) relative to those with no exposure. For active smoking, when the referent group consisted of never smokers who had not been regularly exposed to ETS, the risk increases were more pronounced with an increased number of years of smoking, cigarette pack-years, years since quit smoking, and average number of cigarettes smoked daily. Overall, our results are suggestive of a weak association between pancreatic cancer and ETS. Perhaps more importantly, they suggest that ETS smoking exposures may confound the risk of pancreatic cancer associated with active smoking measures commonly used in epidemiologic studies.

Brain cancer and occupational exposure to magnetic fields among men: results from a Canadian population-based case-control study.

The relationship between occupational exposure to magnetic fields and brain cancer in men was investigated using population-based case-control data collected in eight Canadian provinces. Emphasis was placed on examining the variations in risk across different histological types. A list of occupations was compiled for 543 cases and 543 controls that were individually matched by age. Occupations were categorized according to their average magnetic field exposure through blinded expert review (<0.3, 0.3-<0.6, and > or = 0.6 microT). In total, 133 cases (14%) and 123 controls (12%) were estimated to have at least one occupation whereby magnetic field exposures exceeded 0.3 microT. Odds ratios (OR) were generated using conditional logistic regression, and were adjusted for suspected occupational risk factors for brain cancer. A non-significantly increased risk of brain cancer was observed among men who had ever held a job with an average magnetic field exposure >0.6 microT relative to those with exposures <0.3 microT (OR = 1.33, 95% CI : 0.75-2.36). A more pronounced risk was observed among men diagnosed with glioblastoma multiforme (OR = 5.36, 95% CI : 1.16-24.78). Moreover, a cumulative time weighted index score of magnetic field exposure was significantly related to glioblastoma multiforme (P = 0.02). In contrast, magnetic field exposures were not associated with astrocytoma or other brain cancers. Our findings support the hypothesis that occupational magnetic field exposure increases the risk of glioblastoma multiforme.

Tobacco Use, Occupation, Coffee, Various Nutrients, and Bladder Cancer2

In a Canadian population-based case-control study of 480 males and 152 female case-control pairs, the relative risk for development of bladder cancer for ever used versus never used cigarettes was 3.9 for males and 2.4 for females, with a dose-response relationship in both sexes. A reduced risk was associated with the use of filter cigarettes compared to nonfilter cigarettes. After control for cigarette usage, a significant risk was noted for male pipe smokers. For male ex-smokers the risk after 15 years of no smoking was less than one-half that of current male smokers. Bladder cancer risk was found for workers in the chemical, rubber, photographic, petroleum, medical, and food processing industries among males and for workers occupationally exposed to dust or fumes among both sexes. Bladder cancer risk was elevated for males consuming all types of coffee, regular coffee, and instant coffee and for females consuming instant coffee, but no dose-response relationship was found. Risk was found for males consuming water from nonpublic supples but not for females. No risk was observed in males or females consuming nitrate-containing foods, beverages other than coffee, or fiddlehead greens. Hair dye usage in females and phenacetin usage in males and females carried no risk. Divergent findings by area for aspirin suggested that an overall association was not causal. Reevaluation of the data on artificial sweeteners confirmed a significant bladder cancer risk in males and a dose-response relationship. The cumulated population attributable risk for bladder cancer was 90% for males from cigarette smoking, industrial exposure, and exposure to nonpublic water supplies and 29% for females from cigarette smoking, industrial exposure, and instant coffee consumption.