Meta-analysis of studies on individual consumption of chlorinated drinking water and bladder cancer

Abstract

Study objective: To evaluate whether consumption of chlorinated drinking water is associated with bladder cancer. Design: A bibliographic search was conducted and the authors selected studies evaluating individual consumption of chlorinated drinking water and bladder cancer. The authors extracted from each study risk estimates for intermediate and long term (>40 years) consumption of chlorinated water, stratified by sex when possible, and performed meta-analysis for the two exposure levels. A meta-analysis was also performed of the dose-response regression slopes. Setting: Populations in Europe and North America. Participants: Those included in six case-control studies (6084 incident bladder cancer cases, 10 816 controls) and two cohort studies (124 incident bladder cancer cases) fulfilling the inclusion criteria. Main results: Ever consumption of chlorinated drinking water was associated with an increased risk of bladder cancer in men (combined OR=1.4, 95%CI 1.1 to 1.9) and women (combined OR=1.2, 95%CI 0.7 to 1.8). The combined OR for mid-term exposure in both genders was 1.1 (95% CI 1.0 to 1.2) and for long term exposure was 1.4 (95%CI 1.2 to 1.7). The combined estimate of the slope for a linear increase in risk was 1.13 (95% CI 1.08 to 1.20) for 20 years and 1.27 (95% CI 1.15 to 1.43) for 40 years of exposure in both sexes. Conclusions: This meta-analysis of the best available epidemiological evidence indicates that long term consumption of chlorinated drinking water is associated with bladder cancer, particularly in men. The observed relative risk is only moderately high, but the population attributable risk could be important as the vast majority of the population of industrialised countries is potentially exposed to chlorination byproducts for long time periods.

Overview of Disinfection By-products and Associated Health Effects

“…Inconsistencies among studies were highlighted, particularly with regard to sex and smoking status. A meta-analysis by Villanueva et al (2003) of six case-control and two cohort studies showed a combined relative risk of 1.6 (95 % CI,1.2-2.2) in men and 1.4 (95 % CI 0.6-3.6) in women for more than 40 years of exposure to chlorinated water. An [49,52,53].…”

“…The bladder has been the most frequently evaluated cancer site, including two meta-analyses [49,50] and two pooled analyses [40, 51•]. King (2001) analyzed six casecontrol and one cohort study, including incident cases, ascertainment of residential histories, water exposure, and confounders.…”

Nonsteroidal antiinflammatory drug use and risk of bladder cancer in the health professionals follow‐up study

“…2 Cigarette smoking, 4,5 occupational exposures to aromatic amines 6-8 and schistosomal infections 9,10 have been associated with risk of bladder cancer. Other environmental factors, including selenium intake, 8 chlorination by-products 11,12 and low dose arsenic levels in water sources, 13,14 have also been associated with bladder cancer, but are less well-established.Epidemiologic evidence suggests that use of nonsteroidal antiinflammatory drugs (NSAIDs), particularly aspirin, may lower the risk of several cancers, 15-20 including bladder cancer. 21 Several epidemiologic studies on urinary tract infections, 22,23 indwelling catheters, 24 bladder stones 25 and schistosomiasis 26 all support a role for inflammation in bladder carcinogenesis.…”

“…2 Cigarette smoking, 4,5 occupational exposures to aromatic amines 6-8 and schistosomal infections 9,10 have been associated with risk of bladder cancer. Other environmental factors, including selenium intake, 8 chlorination by-products 11,12 and low dose arsenic levels in water sources, 13,14 have also been associated with bladder cancer, but are less well-established.…”

Effects of household handling on disinfection by- products

“…However, chlorine also reacts with natural organic matter (NOM) present in water, leading to the formation of trihalomethanes (THMs), haloacetic acids (HAAs), halonitromethanes (HNMs) and other disinfection byproducts (DBPs) [1], [2].Carcinogenic and reproductive effects of DBPs have been reported in toxicological and epidemiological studies [3], [4].THMs are regulated because of their potential health risk, and because they act as surrogates for the control of other halogenated DBPs with health concerns. At the USEPA, the sum of four THMs (THM4, i.e., chloroform, bromodichloromethane, dibromochloromethane, bromoform) is regulated at 80μg/L [5].…”