Abstract LB-376: Hormone therapy use and DNA methylation in breast tissue

Abstract

Abstract The association between use of hormone therapy (HT) and breast cancer risk has been consistently replicated in epidemiologic studies, but the biological effects of HT on breast tissue are poorly understood. We hypothesized that postmenopausal exposure to HT leads to changes in DNA methylation in breast tissue. We used fresh frozen samples from the Normal Breast Study (NBS), a hospital based study conducted between 2009 and 2013 at the University of North Carolina in Chapel Hill. Women undergoing breast surgery for reduction mammoplasty, prophylactic resection, or tumor resection donated samples of histologically normal-appearing breast tissue. Out of 474 enrolled participants 106 reported ever using hormone therapy, 37 of which had used it within one year of surgery (classified as current users) and 17 of which had used HT within 1-5 years prior to surgery (classified as recent users). Current and recent users were compared with 36 age frequency-matched controls that had never used HT. Frozen tissue DNA samples from these 90 women were evaluated using the Illumina HumanMethylation450 BeadChip. Genome wide DNA methylation data was analyzed using the reference-free cell mixture method to test for associations between HT-use and the methylation level at each CpG site. In the model we adjusted for SVA derived surrogate variables, to control for unobserved confounders, and multiple comparisons using the false discovery rate (FDR). Although methylation differences between current and never users were small in magnitude (β<0.05), 290 CpGs were significantly differentially methylated (FDR, q<0.05). The top CpG was located in an intronic region of the DDX10 gene (p = 7.9E-10, q = 0.0003), previously known to be translocated in estrogen receptor-negative (ER-) breast cancer. Our results extend the evidence base for hormonally derived epigenetic changes in breast tissue. Citation Format: Sophia Harlid, Zongli Xu, Erin L. Kirk, Lauren E. Wilson, Melissa A. Troester, Jack A. Taylor. Hormone therapy use and DNA methylation in breast tissue. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-376.