Ammons Samantha, Madrigal Jessica M, Manley Cherrel K, Spaur Maya, Hofmann Jonathan N, Sandler Dale P, Freeman Laura E Beane, Ward Mary H, Jones Rena R
Occupational and Environmental Epidemiology Branch (OEEB), Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), National Institutes of Health (NIH), Rockville, Maryland.
Department of Epidemiology, University of North Carolina Chapel Hill Gillings School of Public Health, Chapel Hill, North Carolina.
Environ Epidemiol. 2025 May 13;9(3):e382. doi: 10.1097/EE9.0000000000000382. eCollection 2025 Jun.
N-Nitroso compounds formed endogenously after nitrate/nitrite ingestion cause ovarian cancer in animals. Few epidemiologic studies have evaluated the associations between drinking water nitrate, disinfection by-products (DBPs), and dietary nitrate/nitrite intake with ovarian cancer risk.
We evaluated ovarian cancer risk in relation to drinking water nitrate and DBPs and dietary nitrate/nitrite in the Agricultural Health Study, a cohort of pesticide applicators and their spouses in Iowa and North Carolina (enrollment 1993-1997, N = 33,689). We computed average nitrate-nitrogen and DBPs (total trihalomethanes and haloacetic acids) levels at enrollment addresses on public water supplies using historical monitoring data. We estimated nitrate concentrations in private wells using random forest models. Dietary nitrate/nitrite intakes were estimated from a food frequency questionnaire at follow-up (1999-2003, N = 11,518). We computed hazard ratios (HR) and 95% confidence intervals (CIs) adjusted for age, body mass index, smoking, and menopausal status using Cox regression. We tested the interactions of drinking water nitrate with vitamin C and red meat intake among those with dietary data.
We identified 166 ovarian cancers (enrollment through 2021). Risk was elevated with increasing levels of drinking water nitrate-nitrogen (per 5 mg/L; HR = 1.15; 95% CI: 0.96, 1.39) and total trihalomethanes (per 37 µg/L; HR = 1.06; 95% CI: 1.02, 1.10). Increasing dietary nitrate intake was associated with ovarian cancer risk (per 10 mg/day; HR = 1.08; 95% CI: 1.01, 1.15) but there was no association with dietary nitrite. We found no statistical interactions with vitamin C or red meat intake.
These drinking water and dietary exposures deserve further study as potential novel ovarian cancer risk factors.
摄入硝酸盐/亚硝酸盐后内源性形成的N-亚硝基化合物可导致动物患卵巢癌。很少有流行病学研究评估饮用水硝酸盐、消毒副产物（DBPs）以及膳食硝酸盐/亚硝酸盐摄入量与卵巢癌风险之间的关联。
在农业健康研究中，我们评估了爱荷华州和北卡罗来纳州的一组农药施用者及其配偶（1993 - 1997年入组，N = 33,689）中饮用水硝酸盐和消毒副产物以及膳食硝酸盐/亚硝酸盐与卵巢癌风险的关系。我们利用历史监测数据计算了入组地址公共供水系统中的平均硝酸盐氮和消毒副产物（总三卤甲烷和卤乙酸）水平。我们使用随机森林模型估计了私人井中的硝酸盐浓度。膳食硝酸盐/亚硝酸盐摄入量通过随访时（1999 - 2003年，N = 11,518）的食物频率问卷进行估计。我们使用Cox回归计算了调整年龄、体重指数、吸烟和绝经状态后的风险比（HR）和95%置信区间（CI）。我们在有膳食数据的人群中测试了饮用水硝酸盐与维生素C和红肉摄入量之间的相互作用。
我们确定了166例卵巢癌病例（截至2021年入组）。饮用水硝酸盐氮水平升高（每5mg/L；HR = 1.15；95%CI：0.96,1.39）和总三卤甲烷水平升高（每37μg/L；HR = 1.06；95%CI：1.02,1.10）时，风险升高。膳食硝酸盐摄入量增加与卵巢癌风险相关（每10mg/天；HR = 1.08；95%CI：1.01,1.15）但与膳食亚硝酸盐无关。我们未发现与维生素C或红肉摄入量存在统计学上的相互作用。
作为潜在的新型卵巢癌风险因素，这些饮用水和膳食暴露值得进一步研究。
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