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

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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.