Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.
Environ Int. 2019 May;126:242-251. doi: 10.1016/j.envint.2019.02.010. Epub 2019 Feb 26.
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.
We investigated the relationship between drinking water exposures and incident colorectal cancers in a cohort of postmenopausal women.
Using historical nitrate-nitrogen (NO-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 NO-N and >40 μg/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 NO-N interactions with DBPs and with factors influencing endogenous NOC formation.
We identified 624 colon and 158 rectal cancers (1986-2010) among 15,910 women reporting PWS use >10 years. Ingestion of NO-N from drinking water was not associated with risk. Colon cancer risks were non-significantly associated with the average TTHM levels >17.7 μg/L (HR = 1.13, CI = 0.89-1.44; p = 0.11) and were elevated for any duration of exposure >1/2-MCL. Rectal cancer risks were associated with the highest TTHM levels (HR = 1.71, CI = 1.00-2.92; p = 0.22) but not with years >1/2-MCL. Bromodichloromethane (HR = 1.89, CI = 1.17-3.00; p = 0.09) and trichloroacetic acid (HR = 1.92, CI = 1.20-3.09; p = 0.18) levels were also associated with risk of rectal cancer. We found no evidence of interaction between TTHM and NO-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.
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.
硝酸盐/亚硝酸盐摄入后内源性形成的 N-亚硝基化合物（NOC）和消毒副产物（DBPs）被怀疑是结直肠癌的致癌因素，但这些关联的流行病学证据有限。
我们在一组绝经后妇女队列中调查了饮用水暴露与结直肠癌发病的关系。
利用历史硝酸盐氮（NO-N）测量值和公共供水（PWS）中总三卤甲烷（TTHM）、5 或 6 种卤乙酸（HAAs）总和以及个别 DBP 的估计值，我们计算了平均暴露量和超过美国最大污染物水平一半以上的暴露年限（>1/2-MCL；>5mg/L 的 NO-N 和>40μg/L 的 TTHM）。通过食物频率问卷估计饮食中硝酸盐/亚硝酸盐的摄入量。我们从 Cox 回归模型中估计了危险比（HR）和 95%置信区间（CI）。我们评估了 NO-N 与 DBP 之间以及与影响内源性 NOC 形成的因素之间的相互作用。
在 15910 名报告使用 PWS 超过 10 年的妇女中，我们确定了 624 例结肠癌和 158 例直肠癌（1986-2010 年）。饮用水中摄入的 NO-N 与风险无关。结肠癌风险与平均 TTHM 水平>17.7μg/L 呈非显著相关（HR=1.13，CI=0.89-1.44；p=0.11），与>1/2-MCL 任何持续时间的暴露均升高。直肠癌风险与最高 TTHM 水平相关（HR=1.71，CI=1.00-2.92；p=0.22），但与>1/2-MCL 年数无关。溴二氯甲烷（HR=1.89，CI=1.17-3.00；p=0.09）和三氯乙酸（HR=1.92，CI=1.20-3.09；p=0.18）水平也与直肠癌风险相关。我们没有发现 TTHM 和 NO-N 之间相互作用对两种癌症风险的证据。膳食分析显示，红肉与结肠癌呈正相关，但与加工肉摄入量或特定膳食来源估计的硝酸盐/亚硝酸盐无关。
我们的结果表明，饮用水中 TTHM 的暴露与直肠癌风险增加有关。对于结直肠癌和直肠癌，个别 THMs 和 HAAs 的阳性发现需要在其他研究中复制。我们没有发现硝酸盐总体或亚组与假定更高 NOC 暴露相关的关联。
