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Background: N-nitroso compounds are hypothesized human bladder carcinogens. We investigated ingestion of N-nitroso compound precursors nitrate and nitrite from drinking water and diet and bladder cancer in the New England Bladder Cancer Study.Methods: Using historical nitrate measurements for public water supplies and measured and modeled values for private wells, as well as self-reported water intake, we estimated average nitrate concentrations (mg/L NO3-N) and average daily nitrate intake (mg/d) from 1970 to diagnosis/reference date (987 cases and 1,180 controls). We estimated overall and source-specific dietary nitrate and nitrite intakes using a food frequency questionnaire (1,037 cases and 1,225 controls). We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). We evaluated interactions with factors that may affect N-nitroso compound formation (i.e., red meat, vitamin C, smoking), and with water intake.Results: Average drinking water nitrate concentration above the 95th percentile (>2.07 mg/L) compared with the lowest quartile (≤0.21 mg/L) was associated with bladder cancer (OR = 1.5, 95% CI = 0.97, 2.3; P trend = 0.01); the association was similar for average daily drinking water nitrate intake. We observed positive associations for dietary nitrate and nitrite intakes from processed meat (highest versus lowest quintile OR for nitrate = 1.4, 95% CI = 1.0, 2.0; P trend = 0.04; OR for nitrite = 1.5, 95% CI = 1.0, 2.1; P trend = 0.04, respectively), but not other dietary sources. We observed positive interactions between drinking water nitrate and red meat (P-interaction 0.05) and processed red meat (0.07).Conclusions: Our results suggest the importance of both drinking water and dietary nitrate sources as risk factors for bladder cancer. [ABSTRACT FROM AUTHOR]

In the 1980s, a case–control epidemiologic study was conducted in Iowa (USA) to analyze the association between exposure to disinfection by-products (DBPs) and bladder cancer risk. Trihalomethanes (THMs), the most commonly measured and dominant class of DBPs in drinking water, served as a primary metric and surrogate for the full DBP mixture. Average THM exposure was calculated, based on rough estimates of past levels in Iowa. To reduce misclassification, a follow-up study was undertaken to improve estimates of past THM levels and to re-evaluate their association with cancer risk. In addition, the risk associated with haloacetic acids, another class of DBPs, was examined. In the original analysis, surface water treatment plants were assigned one of two possible THM levels depending on the point of chlorination. The re-assessment considered each utility treating surface or groundwater on a case-by-case basis. Multiple treatment/disinfection scenarios and water quality parameters were considered with actual DBP measurements to develop estimates of past levels. The highest annual average THM level in the re-analysis was 156 μg/L compared to 74 μg/L for the original analysis. This allowed the analysis of subjects exposed at higher levels (> 96 μg/L). The re-analysis established a new approach, based on case studies and an understanding of the water quality and operational parameters that impact DBP formation, for determining historical exposure. [ABSTRACT FROM AUTHOR]

Selenium has been linked to a reduced risk of bladder cancer in some studies. Smoking, a well-established risk factor for bladder cancer, has been associated with lower selenium levels in the body. We investigated the selenium-bladder cancer association in subjects from Maine, New Hampshire, and Vermont in the New England Bladder Cancer Case-Control Study. At interview (2001-2005), participants provided information on a variety of factors, including a comprehensive smoking history, and submitted toenail samples, from which we measured selenium levels.We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271 controls using logistic regression. After controlling for smoking, we saw no evidence of an association between selenium levels and bladder cancer (for fourth quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.77, 1.25). When results were restricted to regular smokers, there appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however, when pack-years of smoking were considered, this association was attenuated (OR = 0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite some reports of an inverse association between selenium and bladder cancer overall, our results, combined with an in-depth evaluation of other studies, suggested that confounding from smoking intensity or duration could explain this association. Our study highlights the need to carefully evaluate the confounding association of smoking in the selenium-bladder cancer association. [ABSTRACT FROM AUTHOR]

A few epidemiologic studies have found that use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with reduced risk of bladder cancer. However, the effects of specific NSAID use and individual variability in risk have not been well studied. We examined the association between NSAIDs use and bladder cancer risk, and its modification by 39 candidate genes related to NSAID metabolism. A population-based case-control study was conducted in northern New England, enrolling 1,171 newly diagnosed cases and 1,418 controls. Regular use of nonaspirin, nonselective NSAIDs was associated with reduced bladder cancer risk, with a statistically significant inverse trend in risk with duration of use (ORs of 1.0, 0.8, 0.6 and 0.6 for <5, 5-9, 10-19 and 20+ years, respectively; ptrend = 0.015). This association was driven mainly by ibuprofen; significant inverse trends in risk with increasing duration and dose of ibuprofen were observed ( ptrend = 0.009 and 0.054, respectively). The reduced risk from ibuprofen use was limited to individuals carrying the T allele of a single nucleotide polymorphism (rs4646450) compared to those who did not use ibuprofen and did not carry the T allele in the CYP3A locus, providing new evidence that this association might be modified by polymorphisms in genes that metabolize ibuprofen. Significant positive trends in risk with increasing duration and cumulative dose of selective cyclooxygenase (COX-2) inhibitors were observed. Our results are consistent with those from previous studies linking use of NSAIDs, particularly ibuprofen, with reduced risk. We observed a previously unrecognized risk associated with use of COX-2 inhibitors, which merits further evaluation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bladder cancer has been linked with long-term exposure to disinfection by-products (DBPs) in drinking water. OBJECTIVES: In this study we investigated the combined influence of DBP exposure and polymorphisms in glutathione S-transferase (GSTT1, GSTZ1) and cytochrome P450 (CYP2E1) genes in the metabolic pathways of selected by-products on bladder cancer in a hospital-based case-control study in Spain. METHODS: Average exposures to trihalomethanes (THMs; a surrogate for DBPs) from 15 years of age were estimated for each subject based on residential history and information on municipal water sources among 680 cases and 714 controls. We estimated effects of THMs and GSTT1, GSTZ1, and CYP2E1 polymorphisms on bladder cancer using adjusted logistic regression models with and without interaction terms. RESULTS: THM exposure was positively associated with bladder cancer: adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.2 (0.8-1.8), 1.8 (1.1-2.9), and 1.8 (0.9-3.5) for THM quartiles 2, 3, and 4, respectively, relative to quartile 1. Associations between THMs and bladder cancer were stronger among subjects who were GSTT1 +/+ or +/- versus GSTT1 null (pinteraction = 0.021), GSTZ1 rs1046428 CT/TT versus CC (pinteraction = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (pinteraction = 0.035). Among the 195 cases and 192 controls with high-risk forms of GSTT1 and GSTZ1, the ORs for quartiles 2, 3, and 4 of THMs were 1.5 (0.7-3.5), 3.4 (1.4-8.2), and 5.9 (1.8-19.0), respectively. CONCLUSIONS: Polymorphisms in key metabolizing enzymes modified DBP-associated bladder cancer risk. The consistency of these findings with experimental observations of GSTT1, GSTZ1, and CYP2E1 activity strengthens the hypothesis that DBPs cause bladder cancer and suggests possible mechanisms as well as the classes of compounds likely to be implicated. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking is a well-established risk factor for bladder cancer. The effects of smoking duration, intensity (cigarettes per day), and total exposure (pack-years); smoking cessation; exposure to environmental tobacco smoke; and changes in the composition of tobacco and cigarette design over time on risk of bladder cancer are unclear. [ABSTRACT FROM PUBLISHER]

We are conducting a collaborative, population-based case-control study in Maine, New Hampshire, and Vermont to investigate the reasons for the elevated bladder cancer mortality in northern New England. Arsenic in drinking water is one of the primary exposures under investigation. To estimate subjects' lifetime exposure to waterborne arsenic, it will be necessary to obtain water samples from private wells that subjects used in the past. We conducted a methodologic study to assess the feasibility of locating and sampling from private wells at subjects' past residences. Ninety-eight New Hampshire residents (mean age 67 years) completed a questionnaire requesting the complete address, dates of occupancy, and drinking water sources for each home lived in since birth. An interviewer then asked subjects for more detailed information about each home to assist in a field search of past homes in the three-state study area of Maine, New Hampshire, and Vermont. Fifty-eight of the 98 subjects indicated that they had used a total of 103 private wells in 95 previous homes located in these three states. We conducted a field search to locate these 95 homes, visited town offices to find the properties on tax maps and obtain the current owners' names and addresses, attempted to obtain permission from the current owners to sample the wells, and collected water samples. In all, 48 (47%) of the 103 past wells in the study area were sampled successfully. The remaining wells were not sampled because the homes were not located (22%) or had been demolished (2%), permission to sample the wells was not obtained (17%), the wells had been destroyed (7%) or could not be found on the grounds of the residence (3%), or for other reasons (2%). Various approaches for improving the success rates for sampling water from private wells are discussed, as is the use of predictive modeling to impute exposures when sampling is not feasible. [ABSTRACT FROM AUTHOR]

Presents a study that investigated the role of occupation and industry in the risk of bladder cancer among employees in Iowa. Background on bladder cancer; Analysis of the risk for bladder cancer by industry and occupation among men and women in the state; Examination of the distribution of age, smoking habits and bladder cancer in men and women.

This article comments on the epidemiological investigation of the correlation between chlorination and the incidence of cancer. As soon as this investigation began, it encountered three hurdles, including the determination which organs might be affected. There has been a general convergence of findings in that cancers of the bladder, colon, and rectum have been associated with various measures of chlorination by-product contamination. An especially challenging aspect of studying environmental contamination and disease is to define and then estimate exposure at the relevant time in a person's life.

Objectives We used data from a large, population-based case-control study in Maine, New Hampshire, and Vermont to examine relationships between occupation, industry and bladder cancer risk. Methods Lifetime occupational histories were obtained by personal interview from 1158 patients newly diagnosed with urothelial carcinoma of the bladder in 2001-2004, and from 1402 population controls. Unconditional logistic regression was used to calculate ORs and 95% CIs, adjusted for demographic factors, smoking and employment in other high-risk occupations. Results Male precision metalworkers and metalworking/plasticworking machine operators had significantly elevated risks and significant trends in risk with duration of employment (precision metalworkers: OR 2.2, 95% CI 1.4 to 3.4, ptrend=0.0065; metalworking/plasticworking machine operators: OR 1.6, 95% CI 1.01 to 2.6, ptrend=0.047). Other occupations/industries for which risk increased significantly with duration of employment included: for men, textile machine operators, mechanics/repairers, automobile mechanics, plumbers, computer systems analysts, information clerks, and landscape industry workers; for women, service occupations, health services, cleaning and building services, management-related occupations, electronic components manufacturing and transportation equipment manufacturing. Men reporting use of metalworking fluids (MWF) had a significantly elevated bladder cancer risk (OR 1.7, 95% CI 1.1 to 2.5). Conclusions Our findings support the hypothesis that some component(s) of MWF may be carcinogenic to the bladder. Our results also corroborate many other previously reported associations between bladder cancer risk and various occupations. More detailed analyses using information from the study's job-specific questionnaires may help to identify MWF components that may be carcinogenic, and other bladder carcinogens associated with a variety of occupations. [ABSTRACT FROM AUTHOR]

Examines the effects of misclassification on risk estimates of chlorinated drinking water and bladder cancer in Iowa. Contamination of water source; Assessment of hologynic organic compounds as byproducts of chlorination; Quantification of environmental exposure.