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Environmental Chemical Body Burden and Prospective Breast Cancer Risk in the Cancer Prevention Study-3 Cohort - CIDR

This study is focused on chemical body burden of per- and poly-fluoroalkyl substances (PFAS), and concomitant risk of developing invasive breast cancer during the menopausal transition. We hypothesized that elevated body-burden levels of these endocrine-disrupting chemicals (EDCs) will increase the risk of developing breast cancer, and that alterations of the methylome will link these chemical exposures and breast cancer.

In Specific Aim 1, using samples and data from a prospective study of women in the American Cancer Society (ACS) Cancer Prevention Study 3 (CPS-3), we are assessing the association between body burden of PFAS during the menopausal transition and subsequent development of invasive breast cancer. The California Environmental Chemistry lab is determining PFAS levels in plasma samples collected 1 to 7 years prior to a diagnosis of invasive breast cancer from 998 ACS CPS-3 participants and 998 matched, cancer-free CPS-3 participants. All subjects were between 40 and 57 years of age when the blood sample was taken.

In Specific Aim 2, studying the same participants, DNA methylation (DNAm) using Infinium MethylationEPIC BeadChips was conducted at Center for Inherited Disease Research (CIDR). We are conducting an epigenome-wide association study (EWAS) to identify DNAm changes associated with levels of PFAS in the cancer-free participants. We then will determine the association between the PFAS-associated DNAm changes and risk of developing breast cancer. The design is a nested case control study within the ACS CPS-3 cohort. Available data include the DNAm data and phenotypic data on case or control status, age at diagnosis of breast cancer, age at blood draw for cases and controls, and self-reported race/ethnicity.