Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Environ Res. 2022 Nov;214(Pt 2):113906. doi: 10.1016/j.envres.2022.113906. Epub 2022 Jul 19.
The epidemiological evidence regarding the carcinogenicity of nitrate and sodium in drinking water is limited, partly because measuring the exposure at the individual level is complex. Most studies have used nitrate in water supplies as a proxy for individual exposure, but dietary intakes and other factors may contribute to the exposure. The present study investigates the factors associated with urinary nitrate and sodium in a high-risk area for esophageal and gastric cancers.
For this cross-sectional study, we used data and samples collected in 2004-2008 during the enrollment phase of the Golestan Cohort Study from a random sample of 349 participants (300 individuals from 24 rural villages and 49 from the city of Gonbad), stratified by average water nitrate in their district, the source of drinking water, and the usual dietary intake of nitrate and sodium. Nitrate, sodium, and creatinine were measured in a spot urine sample collected at the time of interview. We used the provincial cancer registry data to calculate the cumulative incidence rates of esophageal and gastric cancers for each location through June 1, 2020, and used weighted partial Pearson correlation to compare the incidence rates with median urinary nitrate and sodium in each village or the city.
Among 349 participants (mean age±SD: 50.7 ± 8.6 years), about half (n = 170) used groundwater for drinking, and the use of groundwater was significantly more common in high-elevation locations (75.8%). The geometric mean of the creatinine-corrected urinary nitrate concentration was 68.3 mg/g cr (95%CI: 64.6,72.3), and the corresponding geometric mean for urinary sodium was 150.0 mmoL/g cr (95%CI: 139.6,161.1). After adjusting for confounders, urinary nitrate was associated with being a woman, drinking groundwater, and living in high-elevation locations, but not with estimated dietary intake. Urinary sodium concentration was significantly associated with monthly precipitation at the time of sampling but not with elevation or drinking water source. There were significant positive correlations between both median urinary nitrate and sodium in each location and esophageal cancer incidence rates adjusted for sex and age (r = 0.65 and r = 0.58, respectively, p < 0.01), but not with gastric cancer incidence.
In a rural population at high risk for esophageal and gastric cancers, nitrate excretion was associated with living at a higher elevation and using groundwater for drinking. The associations between nitrate and sodium excretion with esophageal cancer incidence warrant future investigation.
关于饮用水中硝酸盐和钠的致癌性的流行病学证据有限，部分原因是个体水平的暴露测量较为复杂。大多数研究都使用供水系统中的硝酸盐作为个体暴露的替代物，但饮食摄入和其他因素可能会影响暴露。本研究旨在调查在食管癌和胃癌高发地区与尿液中硝酸盐和钠相关的因素。
本横断面研究使用了 2004 年至 2008 年戈勒斯坦队列研究入组阶段收集的数据和样本，该研究是在该地区的 24 个农村村庄和戈纳布市的 49 名随机参与者中进行的，按地区平均水硝酸盐、饮用水来源和通常的硝酸盐和钠饮食摄入量进行分层。在访谈时采集了一份尿液样本，测量了硝酸盐、钠和肌酐。我们使用省级癌症登记数据，通过 2020 年 6 月 1 日计算了每个地点食管癌和胃癌的累积发病率，并使用加权部分 Pearson 相关系数比较了每个村庄或城市的中位数尿液硝酸盐和钠与发病率的相关性。
在 349 名参与者（平均年龄±标准差：50.7±8.6 岁）中，约一半（n=170）使用地下水作为饮用水，并且在高海拔地区使用地下水的情况更为常见（75.8%）。经肌酐校正后的尿液硝酸盐浓度的几何均数为 68.3mg/g cr（95%CI：64.6，72.3），尿液钠的相应几何均数为 150.0mmol/g cr（95%CI：139.6，161.1）。在调整了混杂因素后，尿液硝酸盐与女性、饮用地下水和居住在高海拔地区有关，但与估计的饮食摄入量无关。尿液钠浓度与采样时的月降水量显著相关，但与海拔或饮用水源无关。每个地点的中位数尿液硝酸盐和钠与食管癌发病率校正性别和年龄后均呈显著正相关（r=0.65 和 r=0.58，p<0.01），但与胃癌发病率无关。
在食管癌和胃癌高发的农村人群中，硝酸盐的排泄与居住在较高海拔和饮用地下水有关。硝酸盐和钠排泄与食管癌发病率之间的关联值得进一步研究。
