ALTERED BREAST TUMOR DNA METHYLATION: ASSOCIATIONS WITH PARTICIPANT PARITY AND LACTATION IN THE WESTERN NEW YORK EXPOSURES AND BREAST CANCER (WEB) STUDY
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Childbearing has been shown to be protective against breast cancer risk, although there is a transient increase in risk immediately after giving birth [16, 33-36, 51]. There is evidence that epigenetic changes may be one mechanism responsible for this reduction in pregnancy-related breast cancer risk, although the mechanism is not clearly understood. We investigated the association between having borne children (nulliparous/parous) and breastfeeding (never/ever breastfed) together, and independently, with tumor DNA methylation of SCGB3A1, GSTP1, RARB, SYK, FHIT, CDKN2A, CCND2, BRCA1 and SFN. Our case-only analysis utilized tumors from 724 breast cancer cases in the Western New York Exposures and Breast Cancer (WEB) study. Extensive in-person interviews and self-administered questionnaires were used to assess the main predictor variables, parity and breastfeeding. Tumor DNA methylation was quantitatively measured using bisulfite pyrosequencing. Unconditional logistic regression (OR) was used to calculate the odds of tumor DNA methylation in parous versus nulliparous women, and ever versus never breastfed exposure categories. We found that BRCA1 methylation was higher in parous women, OR = 1.59 (95% CI: 1.02 – 2.46). SFN methylation was also higher in parous women after adjusting for both age and years of education, OR = 1.65 (95% CI: 1.01 – 2.69). There was no association between parity and the methylation of CCND2, CDKN2A, FHIT, GSTP1, RARB, SYK, or SCGB3A1. Furthermore, there were no statistically significant associations between breastfeeding and tumor methylation of any gene in this study. Further investigation on the association between parity and tumor methylation of these genes, as well as a wider range of loci, will further help us understand the role of epigenetics as a mechanism explaining parity and breastfeeding in breast cancer risk.