Case-Control Study of Colon and Rectal Cancers and Chlorination By-Products in Treated Water 1

This population-based case-control study was conducted in southern Ontario, Canada from 1992 to 1994 to assess the relationship between chlorination by-products in public water supplies and cancers of the colon and rectum. Interviews providing residence and water source histories were completed by 76% of eligible cancer cases and 72% of eligible controls. Supplemental data from municipal water supplies were used to estimate individual exposure to water source, chlorination status, and byproduct levels as represented by trihalomethanes (THMs) during the 40-year period before the interview. The analyses included 767 colon cases, 661 rectal cases, and 1545 controls with exposure information for at least 30 of these years (75% of subjects with completed interviews). Among males, colon cancer risk was associated with cumulative exposure to THMs, duration of exposure to chlorinated surface water, and duration of exposure to a THM level >50 mg/liter and 75 mg/liter. Males exposed to chlorinated surface water for 35–40 years had an increased risk of colon cancer compared with those exposed for <10 years (odds ratio, 1.53; 95% confidence interval, 1.13–2.09). Males exposed to an estimated THM level of 75 mg/liter for >35 years had double the risk of those exposed for <10 years (odds ratio, 2.10; 95% confidence interval, 1.21–3.66). In contrast, these relationships were not observed among females. No relationship was observed between rectal cancer risk and any of the measures of exposure to chlorination byproducts. The results of this study should be interpreted with caution because they are only partially congruent with the limited amount of literature addressing this issue. Introduction Chlorine is the most commonly used chemical for the disinfection of Canadian water supplies. During the chlorination process, chlorine reacts with organic material in the water to produce a complex mixture of halogenated and nonhalogenated by-products, the concentration and distribution of which vary with characteristics of the raw water and the treatment process (1). A large number of halogenated chemical species have been identified, including THMs, halogenated acetonitriles, halogenated acids, haloketones, and haloaldehydes (2). THMs are the most frequently occurring by-products (3, 4) and are routinely measured in public water supplies, making them a useful marker of the level of chlorination by-products in treated water. The association between water chlorination and bladder cancer has been the focus of several individual-based epidemiological studies. There have been fewer investigations of cancers of the colon and rectum, and results from studies have been inconsistent (5). Differences in study methods and the specific array of by-products present in different geographic areas may contribute to inconsistencies in results. Because information is generally lacking on historical levels of chlorination by-products, most studies have been based on characteristics of water source, such as chlorinated surface water that correlate, albeit imprecisely, with the level of chlorination by-products. This study used estimated THM levels in public water supplies to examine the relationship between risk of cancers of the colon and rectum and exposure to chlorination by-products. Materials and Methods A population-based case-control study of cancers of the bladder, colon, and rectum was conducted. The study methods have been described previously for bladder cancer (6) and will only be summarized here. Subjects. Cases were 30–74-year-old residents of southern Ontario, Canada, with a primary cancer of the colon or rectum (International Classification of Diseases 9 site codes 153 and 154; Ref. 7). Pathology reports routinely submitted to the Ontario Cancer Registry identified 1722 colon and 1530 rectal cancer cases diagnosed between September 1, 1992, and May 1, 1994 who were eligible for the study. Of these, consent was obtained from the physician to contact 2507 patients; the physician could not be identified for 35 patients, 404 patients were recently deceased or too ill to be contacted, and physicians would not give consent for 306 patients. To identify control subjects, households randomly selected from a database of residential telephone listings were contacted and a census of residents was taken. Where eligible residents were identified, one was selected to participate based on freReceived 10/18/99; revised 5/17/00; accepted 5/19/00. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Supported by the Cancer Bureau of the Laboratory Center for Disease Control, Health Canada and also by the National Health Research and Development Program through a fellowship (to W. D. K.). 2 To whom requests for reprints should be addressed, at Department of Community Health and Epidemiology, Abramsky Hall, Queen’s University, Kingston, Ontario, K7L 3N6 Canada; Phone: (613) 533-6000, extension 74735; Fax: (613) 533 6686; E-mail: kingw@post.queensu. ca. 3 The abbreviations used are: THM, trihalomethane; CI, confidence interval; OR, odds ratio. 813 Vol. 9, 813–818, August 2000 Cancer Epidemiology, Biomarkers & Prevention on April 2, 2017. © 2000 American Association for Cancer Research. cebp.aacrjournals. org Downloaded from quency matching to the age-gender distribution of the combined case series (bladder, colon, and rectal cancer cases). Of 10,219 households contacted, 91% provided a census identifying 2768 eligible subjects. Over 90% (n 5 2494) agreed to have a questionnaire mailed to them. Exposure Assessment. A questionnaire was mailed to the participants, and responses were recorded by a subsequent telephone interview. Participants were queried regarding demographics (e.g., sex, date of birth, and education), other potential risk factors (e.g., medical history and usual diet before diagnosis), and information pertaining to the primary exposures of interest (e.g., residence, water source history, and usual water consumption). Volume of tap water consumed was calculated from the reported daily consumption of water and of beverages or foods made with water, 2 years before the interview. A database was created that characterized each water supply in the study area according to source (surface/ground), chlorination status (chlorinated/nonchlorinated), and level of THMs by geographic area and time. This was based on a survey of treatment plants that collected information on water source and characteristics, and treatment practices for the years of operation between 1950 and 1990. Water plant information was obtained for an average day in August in 5-year intervals, and that observation was used to represent water characteristics for the years surrounding that date. A model, based on data from the Ontario Drinking Water Surveillance Program for the years 1986–1992, was developed to predict the THM level in treated water based on water and treatment characteristics recorded in the database and available from the water plant survey. Application of this model using reported source and treatment characteristics provided by the survey resulted in an estimate of THM level for each plant by time period. Water from private wells was assigned a THM concentration of zero because it is not chlorinated. Individual exposures were assigned by linking subject residence and water source information to the relevant treatment plant data by time and geographic area. Exposures occurring over the 40-year-period preceding 2 years before the subject’s interview were considered, and only subjects with $30 years of known water history were included. Duration of exposure to chlorinated surface water and to water with an estimated summer THM level $50 and 75 mg/liter were calculated by summing the number of years in each exposure category. In addition, THM-years, the sum of the products of continuous estimates of the summer THM level and years at that level, was calculated as an estimate of cumulative exposure. Statistical Analyses. ORs were used as estimates of the relative risk. For the exposures of primary interest, unconditional logistic regression was used to obtain ORs and 95% CIs adjusted for potential confounders (8). Tests for trend were based on a likelihood-ratio test conducted by assigning an ordinal value to each level of a categorical variable and treating the variable as continuous in a logistic regression model. A likelihood-ratio test was performed to evaluate the interaction between cumulative THM exposure and volume of water consumed. Age, sex, and dietary intake of energy (total kilocalories) were included in all analyses. Additional potential confounders were identified by using backward stepwise regression to build a parsimonious model predicting risk for each cancer site. The risk factors that were considered for inclusion on the basis of the cancer literature were: body mass index, education, consumption of alcoholic beverages (beer, wine, spirits), coffee consumption, previous medical conditions (history of Crohn’s disease or colitis), and dietary intake of protein, fat, fiber, cholesterol, calcium, and vitamin A. Exclusion of factors from the model was based on a score-test P . 0.10, a conservative criterion that ensured that all factors that might confound the relationship of interest were included in the model.