Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Universitat Pompeu Fabra, Departament de Ciències Experimentals i de la Salut, Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Environ Res. 2015 Feb;137:299-307. doi: 10.1016/j.envres.2014.10.034. Epub 2015 Jan 16.
Nitrate is a widespread contaminant in drinking water and ingested nitrate under conditions resulting in endogenous nitrosation is suspected to be carcinogenic. However, the suggested association between nitrate in drinking water and bladder cancer remains inconsistent. We evaluated the long-term exposure to drinking water nitrate as a risk factor for bladder cancer, considering endogenous nitrosation modifiers and other covariables.
We conducted a hospital-based case-control study of bladder cancer in Spain (1998-2001). Residential histories and water consumption information were ascertained through personal interviews. Historical nitrate levels (1940-2000) were estimated in study municipalities based on monitoring records and water source. Residential histories of study subjects were linked with nitrate estimates by year and municipality to calculate individual exposure from age 18 to recruitment. We calculated odds ratios (OR) and 95% confidence intervals (CI) for bladder cancer among 531 cases and 556 controls with reliable interviews and nitrate exposure information covering at least 70% of years from age 18 to interview.
Average residential levels ranged from 2.1mg/L to 12.0mg/L among regions. Adjusted OR (95%CI) for average residential levels relative to ≤ 5 mg/L were 1.2 (0.7-2.0) for >5-10mg/L and 1.1 (0.6-1.9) for >10mg/L. The OR for subjects with longest exposure duration (>20 years) to highest levels (>9.5mg/L) was 1.4 (0.9-2.3). Stratification by intake of vitamin C, vitamin E, meat, and gastric ulcer diagnosis did not modify these results. A non-significant negative association was found with waterborne ingested nitrate with an OR of 0.7 (0.4-1.0) for >8 vs. ≤ 4 mg/day. Adjustment for several covariables showed similar results to crude analyses.
Bladder cancer risk was inconsistently associated with chronic exposure to drinking water nitrate at levels below the current regulatory limit. Elevated risk is suggested only among subjects with longest exposure duration to the highest levels. No evidence of interaction with endogenous nitrosation modifiers was observed.
硝酸盐是饮用水中的一种广泛存在的污染物，在导致内源性亚硝化的条件下摄入的硝酸盐被怀疑具有致癌性。然而，饮用水中硝酸盐与膀胱癌之间的关联仍不一致。我们评估了长期暴露于饮用水硝酸盐作为膀胱癌的危险因素，同时考虑了内源性亚硝化修饰剂和其他协变量。
我们在西班牙进行了一项基于医院的膀胱癌病例对照研究（1998-2001 年）。通过个人访谈确定了居住史和水的消耗量信息。根据监测记录和水源，在研究的城市估计了 1940-2000 年的历史硝酸盐水平。根据年份和城市，将研究对象的居住史与硝酸盐的估计值联系起来，以计算他们从 18 岁到招募时的个体暴露情况。我们计算了 531 例病例和 556 例对照的比值比（OR）和 95%置信区间（CI），这些病例和对照的访谈和硝酸盐暴露信息至少覆盖了他们从 18 岁到访谈时的 70%的年份。
各地区的平均住宅硝酸盐水平从 2.1mg/L 到 12.0mg/L 不等。相对于 ≤5mg/L，调整后的 OR（95%CI）为>5-10mg/L（1.2[0.7-2.0]）和>10mg/L（1.1[0.6-1.9]）。暴露时间最长（>20 年）和最高水平（>9.5mg/L）的受试者的 OR 为 1.4（0.9-2.3）。按维生素 C、维生素 E、肉类摄入量和胃溃疡诊断进行分层并没有改变这些结果。与饮水摄入的硝酸盐呈负相关，OR 为 0.7（0.4-1.0），>8mg/d 与 ≤4mg/d 相比。对几个协变量进行调整后，结果与原始分析相似。
膀胱癌风险与低于现行监管限值的饮用水硝酸盐慢性暴露不一致相关。仅在暴露于最高水平时间最长的受试者中发现风险升高。没有观察到与内源性亚硝化修饰剂的相互作用的证据。
