Donat-Vargas Carolina, Kogevinas Manolis, Castaño-Vinyals Gemma, Pérez-Gómez Beatriz, Aragonés Nuria, Guevara Marcela, Gómez-Acebo Inés, Molina Antonio, Fernandez-Tardon Guillermo, Vanaclocha-Espí Mercedes, Molina-Barceló Ana, Moreno Victor, Pollan Marina, Villanueva Cristina M
ISGlobal, Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Environ Health Perspect. 2025 May;133(5):57014. doi: 10.1289/EHP15039. Epub 2025 May 22.
Disinfection byproducts and -nitroso compounds (NOC) formed endogenously after nitrate ingestion have been shown to be carcinogenic in animal studies, but epidemiological evidence is limited, especially in relation to gastric cancer.
We evaluated the association between drinking water exposure to nitrate and trihalomethanes (THMs) and gastric cancer in a multicase-control study conducted in Spain (MCC-Spain).
In 2008-2013, 254 hospital-based incident gastric cancer cases and 2,365 population-based controls were recruited, providing information on residential histories and type of water consumed. Adult lifetime average nitrate and THM levels in residences from age 18 until 2 years before the interview were estimated and linked with water consumption information to calculate waterborne ingested nitrate, brominated (Br)-THMs, and chloroform. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression, with adjustment for potential confounders. We assessed the effect modification by factors influencing endogenous NOC formation.
Median [percentile 25th (P)-percentile 75 (P)] () lifetime waterborne ingested nitrate (), Br-THMs (), and chloroform () were 2.7 (1.4-5.6), 3.8 (1.5-8.1), and 12.2 (4.0-23.7), respectively, in cases and 3.8 (1.8-8.5), 5.7 (2.6-19.2), and 12.9 (4.6-24.5) in controls, respectively. Adjusted OR (95% CI) for gastric cancer comparing nitrate intake vs. (percentile 80th, P) was 1.42 (0.88, 2.29). This association was more pronounced among participants with low consumption of vegetables [2.24 (1.02, 4.91)], vitamin C [2.10 (0.94, 4.71)], and vitamin E [2.81 (1.16, 6.78)] and among those with high consumption of alcohol [2.78 (0.98, 7.93)] or processed meat [1.91 (0.97, 3.75)]. When stratified by age, the association only remained in the years of age group (median 73 years of age). OR for gastric cancer comparing Br-THM ingestion th percentile was 0.65 (0.33, 1.28) and for chloroform was 1.36 (0.87, 2.14). Comparable ORs were found for residential concentrations.
Long-term waterborne nitrate exposure below regulatory limits may increase gastric cancer risk among older adults and in those with poor dietary patterns. These findings need to be confirmed by cohort studies with larger sample sizes. https://doi.org/10.1289/EHP15039.
硝酸盐摄入后内源性形成的消毒副产物和亚硝基化合物（NOC）在动物研究中已被证明具有致癌性，但流行病学证据有限，尤其是与胃癌相关的证据。
在西班牙开展的一项多病例对照研究（MCC-西班牙研究）中，我们评估了饮用水中硝酸盐和三卤甲烷（THM）暴露与胃癌之间的关联。
在2008年至2013年期间，招募了254例基于医院的新发胃癌病例和2365例基于人群的对照，收集他们的居住史和所用水的类型信息。估算了从18岁到访谈前2年期间住所内成人一生平均硝酸盐和THM水平，并将其与用水信息相关联，以计算经水摄入的硝酸盐、溴化（Br）-THM和氯仿量。使用逻辑回归估计比值比（OR）和95%置信区间（CI），并对潜在混杂因素进行调整。我们评估了影响内源性NOC形成的因素对效应的修饰作用。
病例组经水摄入的一生硝酸盐量[第25百分位数（P）-第75百分位数（P）]（）、Br-THM量（）和氯仿量（）的中位数分别为2.7（1.4 - 5.6）、3.8（1.5 - 8.1）和12.2（4.0 - 23.7），对照组分别为3.8（1.8 - 8.5）、5.7（2.6 - 19.2）和12.9（4.6 - 24.5）。比较硝酸盐摄入量处于第80百分位数（P）与（）时，胃癌的调整后OR（95%CI）为1.42（0.88，2.29）。这种关联在蔬菜摄入量低[2.24（1.02，4.91）]、维生素C摄入量低[2.10（0.94，4.71）]、维生素E摄入量低[2.81（1.16，6.78）]的参与者以及酒精摄入量高[2.78（0.98，7.93）]或加工肉类摄入量高[1.91（0.97，3.75）]的参与者中更为明显。按年龄分层时，该关联仅在年龄≥65岁组（中位年龄73岁）中存在。比较Br-THM摄入量处于第80百分位数时胃癌的OR为0.65（0.33，1.28），氯仿的OR为1.36（0.87，2.14）。居住浓度的OR与之相似。
长期经水暴露于低于监管限值的硝酸盐可能会增加老年人以及饮食模式不良者患胃癌的风险。这些发现需要通过更大样本量的队列研究来证实。https://doi.org/10.1289/EHP15039。
