Ingested nitrate, disinfection by-products, and risk of colon and rectal cancers in the Iowa Women's Health Study cohort

Background: N-nitroso compounds (NOC) formed endogenously after nitrate/nitrite ingestion and disinfection by-products (DBPs) are suspected colorectal carcinogens, but epidemiologic evidence of these associations is limited. Objectives: We investigated the relationship between drinking water exposures and incident colorectal cancers in a cohort of postmenopausal women. Methods: Using historical nitrate-nitrogen (NO3-N) measurements and estimates of total trihalomethanes (TTHM), the sum of 5 or 6 haloacetic acids (HAAs), and individual DBPs in public water supplies (PWS), we computed average exposures and years of exposure above one-half the U.S. maximum contaminant level (> 1/2-MCL; > 5 mg/L NO3-N and >40 mu g/L TTHM). Nitrate/nitrite intakes from dietary sources were estimated using a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox regression models. We assessed NO3-N interactions with DBPs and with factors influencing endogenous NOC formation. Results: We identified 624 colon and 158 rectal cancers (1986-2010) among 15,910 women reporting PWS use > 10 years. Ingestion of NO3-N from drinking water was not associated with risk. Colon cancer risks were non-significantly associated with the average TTHM levels > 17.7 mu g/L (HRQ5vsQ1 = 1.13, CI = 0.89-1.44; p(trend) = 0.11) and were elevated for any duration of exposure > 1/2-MCL. Rectal cancer risks were associated with the highest TTHM levels (HRQ5vsQ1 = 1.71, CI = 1.00-2.92; p(trend) = 0.22) but not with years > 1/2-MCL. Bromodichloromethane (HRQ4vsQ1 = 1.89, CI = 1.17-3.00; p(trend) = 0.09) and trichloroacetic acid (HRQ4vsQ1 = 1.92, CI = 1.20-3.09; p(trend) = 0.18) levels were also associated with risk of rectal cancer. We found no evidence of interaction between TTHM and NO3-N on the risk of either cancer. Dietary analyses yielded a positive colon cancer association with red meat, but not with processed meat intake or estimated nitrate/nitrite from specific dietary sources. Conclusions: Our results suggest that exposure to TTHM in drinking water is associated with increased risk of rectal cancer. Positive findings for individual THMs and HAAs for both colon and rectal cancers require replication in other studies. We found no associations for nitrate overall or in subgroups with presumed higher NOC exposure.