A nested case-control study of circulating per- and polyfluoroalkyl substances (PFAS) and ovarian and endometrial cancers in the PLCO Cancer Screening Trial

目前的知识表明，PFAS暴露在美国普通人群中仍然很普遍，令人信服的生殖致癌机制证据，以及与卵巢癌和子宫内膜癌的发生有关的提示性流行病学证据，为评估PFAS暴露在卵巢和子宫内膜癌风险中的作用提供了理由。为了更好地了解全氟辛酸和其他全氟辛烷磺酸是否是卵巢和子宫内膜癌的致癌物，我们建议在PLCO癌症筛查试验中对299例卵巢癌和409例子宫内膜癌患者进行一项嵌套的病例对照研究，研究对象为299例卵巢癌和409例子宫内膜癌患者。这将是迄今为止关于全氟辛烷磺酸暴露与卵巢和子宫内膜癌风险的最大规模的研究，也是第一次调查它们与其他全氟辛烷磺酸的关系。这也将是第一项通过测量诊断前血清浓度来直接评估接触这些化学品的研究。鉴于这些优势，这项研究将极大地促进未来对这些化学物质的致癌性的评估。

Current knowledge that PFAS exposure remains widespread in the general U.S. population, compelling mechanistic evidence for reproductive carcinogenesis, and suggestive epidemiologic evidence of an association with the development of ovarian and endometrial cancers provide justification for evaluating the role of PFAS exposure in ovarian and endometrial cancer risk. To better understand whether PFOA and other PFAS are ovarian and endometrial carcinogens, we propose to conduct a nested case-control study of pre-diagnostic circulating PFAS serum levels among 299 ovarian and 409 endometrial cancer cases with a shared control group within the PLCO Cancer Screening Trial. This will be the largest study of PFOA exposure and ovarian and endometrial cancer risk to date and the first to investigate their associations with other PFAS. It will also be the first study to directly assess exposure to these chemicals through the measurement of pre-diagnostic concentrations in serum. Given these strengths, this study will greatly inform future evaluations of the carcinogenicity of these chemicals.