AS769 - Serum concentrations of per- and polyfluoroalkyl substances and ovarian cancer risk: A nested case-control study in the Women’s Health Initiative

Investigator Names and Contact Information

Rena Jones

Introduction/Intent

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals that have been used widely in industrial and consumer products since the 1940s. Although certain legacy PFAS—including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS)—have been phased out of use in the U.S. since the early 2000s, these “forever chemicals” persist in the environment and continue to be detected in the sera of the U.S. population. Some PFAS exhibit endocrine-disrupting properties, and therefore may play a role in the development of hormone-sensitive cancers. Recent work by our team suggests that several PFAS, particularly PFOS and its precursor 2-N-methyl-perfluorooctane sulfonamido acetic acid (MeFOSAA), may be associated with risk of ovarian cancer, a relatively rare but often fatal malignancy with few established environmental risk factors. To date, only one prospective study, conducted by our team, has evaluated PFAS–ovarian cancer associations using sera collected prior to cancer diagnosis, underscoring the need for further investigation.

We propose a nested case-control study within the Women’s Health Initiative–Observational Study (WHI-OS), a large multicenter prospective cohort of postmenopausal women across the U.S., to investigate associations between prediagnostic serum concentrations of seven commonly detected PFAS [PFOA, PFOS, MeFOSAA, perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA)] and risk of ovarian cancer. This study will include all 699 incident invasive ovarian cancer cases diagnosed through February 2025 within the WHI-OS, as well as 699 individually matched controls. PFAS concentrations will be measured in serum samples (250 µL) collected at the WHI-OS baseline visit (1993-1998). To our knowledge, this will be the largest study to date to directly assess prediagnostic circulating PFAS levels in relation to ovarian cancer risk.

SPECIFIC AIMS

Aim 1: To evaluate associations between prediagnostic serum concentrations of PFAS (PFOA, PFOS, MeFOSAA, PFHxS, PFNA, PFDA, and PFUnDA) and risk of ovarian cancer.

• Secondary Aim 1a: To evaluate associations between prediagnostic serum PFAS concentrations and risk of ovarian cancer by histologic subtype, with a focus on high-grade serous ovarian cancer and exploratory analyses of rarer histotypes (i.e., endometrioid, mucinous, and clear cell).

Aim 2: To evaluate associations between prediagnostic serum PFAS concentrations and risk of ovarian cancer by age at blood collection and time since menopausal onset.