Methylation biomarkers of polybrominated diphenyl ethers (PBDEs) and association with breast cancer risk at the time of menopause

• Published in: Environment international Vol. 156; p. 106772
• Main Authors: Ding, Yuan Chun, Hurley, Susan, Park, June-Soo, Steele, Linda, Rakoff, Michele, Zhu, Yun, Zhao, Jinying, LaBarge, Mark, Bernstein, Leslie, Chen, Shiuan, Reynolds, Peggy, Neuhausen, Susan L
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.11.2021; Elsevier
• Subjects: Adult; Biomarkers; Breast cancer; Breast Neoplasms - genetics; DNA Methylation; Epigenesis, Genetic; EWAS; Female; Halogenated Diphenyl Ethers - toxicity; Humans; Menopause; Middle Aged; PBDEs; DNA methylation; Biomarkers; Breast cancer; EWAS; PBDEs
• ISSN: 0160-4120; 1873-6750
• DOI: 10.1016/j.envint.2021.106772

•Conducted an EWAS of PBDE serum levels.•Identified DNA methylation biomarkers of PBDE blood serum levels.•PBDE-associated blood DNA methylation associated with breast cancer risk at menopause.•Environmental chemicals and risk of breast cancer at the menopausal transition.•PBDE serum levels and association with methylation changes in hormone-pathway genes. Exposure to polybrominated diphenyl ethers (PBDEs) may influence risk of developing post-menopausal breast cancer. Although mechanisms are poorly understood, epigenetic regulation of gene expression may play a role. To identify DNA methylation (DNAm) changes associated with PBDE serum levels and test the association of these biomarkers with breast cancer risk. We studied 397 healthy women (controls) and 133 women diagnosed with breast cancer (cases) between ages 40 and 58 years who participated in the California Teachers Study. PBDE levels were measured in blood. Infinium Human Methylation EPIC Bead Chips were used to measure DNAm. Using multivariable linear regression models, differentially methylated CpG sites (DMSs) and regions (DMRs) associated with serum PBDE levels were identified using controls. For top-ranked DMSs and DMRs, targeted next-generation bisulfite sequencing was used to measure DNAm for 133 invasive breast cancer cases and 301 age-matched controls. Conditional logistic regression was used to evaluate associations between DMSs and DMRs and breast cancer risk. We identified 15 DMSs and 10 DMRs statistically significantly associated with PBDE levels (FDR < 0.05). Methylation changes in a DMS at BMP8B and DMRs at TP53 and A2M-AS1 were statistically significantly (FDR < 0.05) associated with breast cancer risk. We show for the first time that serum PBDE levels are associated with differential methylation and that PBDE-associated DNAm changes in blood are associated with breast cancer risk.