Longitudinal assessment of nitrate and trihalomethanes in drinking-water and breast cancer in the CONSTANCES cohort: a prospective population-based study in France

Nitrate and trihalomethanes (THMs) in drinking water are widespread and potential human carcinogens. We evaluated the association between time-varying exposure to nitrate and THMs in drinking water and female breast cancer (BC) among adults from CONSTANCES, a large French population-based prospective cohort. Our analysis included 26,669 women (18.5-72.5 years old) enrolled in 2012-2020, followed until 2021, with information on residential history, type of water consumed, type of filter used, and bathing and showering frequency. We used water quality data for 2004-2020 from the drinking surveillance national database (SISE-Eaux). Annual median concentrations of nitrate, chloroform, chlorodibromomethane, bromodichloromethane, and bromoform at the participants' residential addresses were estimated. Waterborne ingested exposure was estimated considering type of water, filter used, and liters/day consumed. Estimated exposure in showers and baths combined residential concentrations with showers/baths duration and frequency. Incident BC cases were ascertained in the French national health data system (SNDS) for 2012-2021. Extended Cox models with attained age as time-scale and time-varying weighted average exposures, adjusted for individual and area-level covariables, were used to estimate hazard ratios (HR) and confidence intervals (CI) by exposure tertiles. Average age at enrolment was 49.3 years, and median exposure window was 13 years. Median follow-up was 5 years (153,742 person-years), resulting in 437 new BC diagnoses. Median residential nitrate, brominated (Br)-THMs and chloroform concentrations were, respectively, 15.8 mg/L, 14.2 μg/L, and 2.7 μg/L. HR (95 %CI) of BC associated with waterborne ingested nitrate (mg/day) for the second (>4.8-15.1) and third tertile (>15.1) compared to the first (≤4.8) were 1.35 (1.01-1.81) and 1.51 (1.10-2.07), respectively. Residential THM concentrations were not associated with BC, however HR (95 %CI) of BC for showering and bathing Br-THMs exposure (μg/L × min/day) was 1.18 (0.84-1.64) for the third (>125) vs. first tertile (≤51.5). Findings suggest that ingested nitrate could be a risk factor of BC.