Dataset Information

Drinking Water Disinfection Byproducts, Ingested Nitrate, and Risk of Endometrial Cancer in Postmenopausal Women.

ABSTRACT:

Background

Disinfection byproducts (DBPs) and N-nitroso compounds (NOC), formed endogenously after nitrate ingestion, are suspected endometrial carcinogens, but epidemiological studies are limited.

Objectives

We investigated the relationship of these exposures with endometrial cancer risk in a large prospective cohort.

Methods

Among postmenopausal women in the Iowa Women's Health Study cohort, we evaluated two major classes of DBPs, total trihalomethanes (TTHM) and five haloacetic acids (HAA5), and nitrate-nitrogen (NO3-N) in public water supplies (PWS) in relation to incident primary endometrial cancer (1986-2014). For women using their PWS >10y at enrollment (n=10,501; cases=261), we computed historical averages of annual concentrations; exposures were categorized into quantiles and when possible ≥95th percentile. We also computed years of PWS use above one-half the U.S. maximum contaminant level (>½ MCL; 40μg/L TTHM; 30μg/L HAA5; 5mg/L NO3-N). Dietary nitrate/nitrite intakes were estimated from a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) via Cox models adjusted for age, endometrial cancer risk factors [e.g., body mass index, hormone replacement therapy (HRT)], and mutually adjusted for DBPs or NO3-N. We evaluated associations for low-grade (cases=99) vs. high-grade (cases=114) type I tumors. We assessed interactions between exposures and endometrial cancer risk factors and dietary factors influencing NOC formation.

Results

Higher average concentrations of DBPs (95th percentile: TTHM ≥93μg/L, HAA5 ≥49μg/L) were associated with endometrial cancer risk (TTHM: HR95vsQ1=2.19, 95% CI: 1.41, 3.40; HAA5: HR95vsQ1=1.84, 95% CI: 1.19, 2.83; ptrend<0.01). Associations were similarly observed for women greater than median years of PWS use with levels >½ MCL, in comparison with zero years (TTHM: HR36+vs0y=1.61, 95% CI: 1.18, 2.21; HAA5: HR38+vs0y=1.85, 95% CI: 1.31, 2.62). Associations with DBPs appeared stronger for low-grade tumors (TTHM: HRQ4vsQ1=2.12, 95% CI: 1.17, 3.83; p-trend=0.008) than for high-grade tumors (TTHM: HRQ4vsQ1=1.40, 95% CI: 0.80, 2.44; p-trend=0.339), but differences were not statistically significant (p-heterogeneity=0.43). Associations with TTHM were stronger among ever HRT users than non-HRT users (p-interaction<0.01). We observed no associations with NO3-N in drinking water or diet.

Discussion

We report novel associations between the highest DBP levels and endometrial cancer for our Iowa cohort that warrant future evaluation. https://doi.org/10.1289/EHP10207.

SUBMITTER: Medgyesi DN

PROVIDER: S-EPMC9138501 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Drinking Water Disinfection Byproducts, Ingested Nitrate, and Risk of Endometrial Cancer in Postmenopausal Women.

Medgyesi Danielle N DN Trabert Britton B Sampson Joshua J Weyer Peter J PJ Prizment Anna A Fisher Jared A JA Beane Freeman Laura E LE Ward Mary H MH Jones Rena R RR

Environmental health perspectives 20220527 5

<h4>Background</h4>Disinfection byproducts (DBPs) and <i>N</i>-nitroso compounds (NOC), formed endogenously after nitrate ingestion, are suspected endometrial carcinogens, but epidemiological studies are limited.<h4>Objectives</h4>We investigated the relationship of these exposures with endometrial cancer risk in a large prospective cohort.<h4>Methods</h4>Among postmenopausal women in the Iowa Women's Health Study cohort, we evaluated two major classes of DBPs, total trihalomethanes (TTHM) and f ...[more]

PMID: 35622390

Similar Datasets

Project description:Nitrate is a drinking water contaminant arising from agricultural sources, and it is a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens.We investigated the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women.We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) > 10 years (n = 15,577), we estimated average nitrate (NO3-N) and total trihalomethane (TTHM) levels and the number of years exceeding one-half the maximum contaminant level (NO3-N: 5 mg/L, TTHM: 40 ?g/mL) from historical monitoring data. We computed hazard ratios (HRs) and 95% confidence intervals (CIs), and assessed nitrate interactions with TTHM and with modifiers of NOC formation (smoking, vitamin C).We identified 258 bladder cancer cases, including 130 among women > 10 years at their PWS. In multivariable-adjusted models, we observed nonsignificant associations among women in the highest versus lowest quartile of average drinking water nitrate concentration (HR = 1.48; 95% CI: 0.92, 2.40; ptrend = 0.11), and we found significant associations among those exposed ? 4 years to drinking water with > 5 mg/L NO3-N (HR = 1.62; 95% CI: 1.06, 2.47; ptrend = 0.03) compared with women having 0 years of comparable exposure. TTHM adjustment had little influence on associations, and we observed no modification by vitamin C intake. Relative to a common reference group of never smokers with the lowest nitrate exposures, associations were strongest for current smokers with the highest nitrate exposures (HR = 3.67; 95% CI: 1.43, 9.38 for average water NO3-N and HR = 3.48; 95% CI: 1.20, 10.06 and ? 4 years > 5 mg/L, respectively). Dietary nitrate and nitrite intakes were not associated with bladder cancer.Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women. Citation: Jones RR, Weyer PJ, DellaValle CT, Inoue-Choi M, Anderson KE, Cantor KP, Krasner S, Robien K, Beane Freeman LE, Silverman DT, Ward MH. 2016. Nitrate from drinking water and diet and bladder cancer among postmenopausal women in Iowa. Environ Health Perspect 124:1751-1758;?http://dx.doi.org/10.1289/EHP191.

Dataset Information

Drinking Water Disinfection Byproducts, Ingested Nitrate, and Risk of Endometrial Cancer in Postmenopausal Women.

Background

Objectives

Methods

Results

Discussion

Publications

Drinking Water Disinfection Byproducts, Ingested Nitrate, and Risk of Endometrial Cancer in Postmenopausal Women.

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