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A nested case-control study of circulating per- and polyfluoroalkyl substances (PFAS) and ovarian and endometrial cancers in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Principal Investigator
Name
Rena Jones
Degrees
PhD
Institution
National Cancer Institute
Position Title
NIH investigator
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2019-1010
Initial CDAS Request Approval
Dec 27, 2019
Title
A nested case-control study of circulating per- and polyfluoroalkyl substances (PFAS) and ovarian and endometrial cancers in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
Summary
We are proposing the first prospective investigation of circulating PFAS levels and risk of ovarian and endometrial cancers in a population-based cohort, and the largest investigation of its kind to date. Limited evidence suggests that perfluorooctanoic acid (PFOA), one of the most commonly produced and well-studied PFAS, is associated with increased risk of ovarian cancer. An in vitro study has demonstrated that PFOA stimulates ovarian cancer cell migration. However, the only previous epidemiologic study of PFOA and ovarian cancer relied on an indirect exposure estimate and had small numbers of exposed cases. Other PFAS beyond PFOA have not yet been evaluated in relation to ovarian cancer. In contrast, no previous studies have evaluated the association between PFAS and endometrial cancer.

This will be the first study to directly assess personal exposure to PFAS through serologic testing in samples collected prior to diagnosis of ovarian and endometrial cancers. PFAS have long half-lives in serum, thus are ideally suited for exposure characterization based on levels observed in banked biospecimens. With ~300 ovarian cancer cases and ~400 endometrial cancers and an equivalent number of individually matched controls, the proposed study has a substantially larger sample size relative to prior ovarian cancer studies. This will enhance statistical power and allow us to conduct analyses stratified by participant characteristics that have not been possible before. The proposed study is further innovative for its evaluation of other PFAS in addition to PFOA, and its conduct within a large population-based and geographically diverse U.S. cohort. As such, this investigation has the potential to inform future evaluations of the carcinogenicity of PFOA and to extend our understanding to other PFAS that have not yet been evaluated.
Aims

Aim 1: Evaluate the association between circulating PFAS levels and ovarian cancer risk in PLCO
Aim 2: Evaluate the association between circulating PFAS levels and endometrial cancer risk in PLCO

Collaborators

Rena Jones (OEEB)
Britton Trabert (National Cancer Institute)
Jonathan Hofmann (National Cancer Institute)
Jared Fisher (National Cancer Institute)
Danielle Medgyesi (National Cancer Institute)
Joshua Sampson (National Cancer Institute)

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