Hexavalent chromium and stomach cancer: a systematic review and meta-analysis

Hexavalent chromium [Cr(VI)] is known to cause lung cancer in workers of certain industries, but an association with stomach cancer is uncertain and widely debated. Systematic review and meta-analyses were conducted to assess the risk of stomach cancer mortality/morbidity in humans and experimental animals exposed to Cr(VI). In accordance with the protocol (PROSPERO #CRD4201605162), searches in PubMed and Embase®, and reviews of secondary literature bibliographies, were used to identify eligible studies. Critical appraisal of internal validity and qualitative integration were carried out using the National Toxicology Program’s Office of Health Assessment and Translation (OHAT) approach; meta-analyses were conducted based on the occupational data (the only data suitable for quantitative assessment). Forty-seven publications (3 animal, 44 occupational, 0 non-occupational) met the eligibility criteria. Stomach cancer was only observed in one high risk of bias animal study, and in the low risk of bias studies no stomach cancer was observed. Thus, confidence in this evidence base is high. Environmental epidemiology studies did not meet eligibility criteria because exposure and outcome were not measured at the individual level. Meta-analyses of human data resulted in overall meta relative risks of 1.08 (95% CI: 0.96–1.21) including all studies and 1.03 (95%CI: 0.84–1.26) excluding studies associated with the highest risk of bias. Because most occupational studies have high risk of bias for confounding and exposure domains, the overall confidence in this evidence base is low to moderate. Combining the streams of evidence per the OHAT approach, Cr(VI) does not pose a stomach cancer hazard in humans.六价铬（Hexavalent chromium, Cr(VI)）已被证实可引发特定行业从业者罹患肺癌，但其与胃癌的关联尚不明确且存在广泛争议。本研究开展系统综述与荟萃分析，以评估六价铬暴露人群及实验动物的胃癌死亡风险与发病风险。按照预先注册的研究方案（PROSPERO编号：CRD4201605162），研究人员在PubMed及Embase®数据库中进行文献检索，并梳理二次文献的参考文献列表以筛选符合纳入标准的研究。采用美国国家毒理学项目（National Toxicology Program, NTP）下属健康评估与翻译办公室（Office of Health Assessment and Translation, OHAT）的方法，对研究的内部效度开展严格评价并进行定性整合；针对职业暴露数据（唯一适用于定量评估的数据集）开展荟萃分析。最终共有47篇文献符合纳入标准，其中动物实验研究3篇、职业暴露研究44篇、非职业暴露研究0篇。仅在1项偏倚风险较高的动物实验中观察到胃癌发生，而偏倚风险较低的动物实验未观察到胃癌，因此该证据体系的置信度较高。环境流行病学研究因未在个体水平测量暴露与结局指标，未达到纳入标准。对人类数据的荟萃分析结果显示，纳入全部研究时的合并相对风险为1.08（95%置信区间：0.96–1.21）；排除偏倚风险最高的研究后，合并相对风险为1.03（95%置信区间：0.84–1.26）。由于多数职业研究在混杂因素与暴露评估维度存在较高偏倚风险，该证据体系的整体置信度处于中低水平。依据OHAT方法整合各类证据后，可认为六价铬不会对人类产生胃癌致癌危害。