Exposures to drinking water contaminants in community water systems and risk of ovarian cancer in the California Teachers Study cohort

Several drinking water contaminants are known or suspected carcinogens; however, there are only a few investigations of drinking water exposures and ovarian cancer. We evaluated associations between regulated contaminants in community water systems (CWS) and ovarian cancer risk in the California Teachers Study, a prospective cohort of female California educators. Participants were cancer-free, without bilateral oophorectomy, living in California at baseline (1995-1996) with geocoded addresses linked to a CWS (N=91,127, 92%), with follow-up through 2020 (mean=19.0 years). Among participants with a residential duration at enrollment of at least 10 years, we computed 15-year (1990-2005) averages of log2-transformed arsenic, nitrate, total trihalomethanes (TTHM) (N=59,881), and uranium concentrations (N=56,314). We estimated hazard ratios (HRs, 95% CIs) for all epithelial ovarian cancers (n=424) and the high-grade serous histotype (n=203), using Cox proportional hazards regression, adjusting for age, body mass index, menopause status, oral contraceptive use, and parity. We evaluated the mixture effect (per IQR in log2 concentrations), using quantile-based g-computation. Almost all women (>99%) had average exposures below regulatory limits for all contaminants. In single contaminant analyses, a doubling in average uranium concentrations was associated with all ovarian cancer (HRperlog2=1.09, CI 1.02-1.16), whereas a doubling in nitrate was associated with the high-grade serous histotype (HRperlog2=1.09, CI 1.02-1.17). Findings were similar in models adjusted for other contaminants. We observed positive but imprecise associations for arsenic and TTHM in single-contaminant and contaminant-adjusted analyses. HRs per increase in the mixture were 1.39 (1.00, 1.94) and 1.75 (1.09, 2.83), for all ovarian cancer and the high-grade serous histotype, respectively. Uranium was the largest contributor (55%) to the mixture effect for all ovarian cancer, and nitrate was the largest contributor (46%) for the high-grade serous histotype. Novel associations between drinking water contaminants and ovarian cancer risk at levels below regulatory limits warrant further investigation. https://doi.org/10.1289/EHP16582.