Abstract 2772: Hormone replacement therapy and genome-wide DNA methylation among post-menopausal women

Hormone replacement therapy (HRT) has been associated with increased risks of cancers of the breast, ovary, endometrium and colon. The exact mechanism underlying these associations remains unknown, though changes to DNA methylation have been suggested to play a role. To explore this compelling mechanism, we examined genome-wide DNA methylation in blood among 92 women with and without a history of long-term HRT use that were recruited as controls for a previous case-control study of breast cancer. HRT exposure was defined as estrogen use for at least 10 years among women with hysterectomy (n = 23) and as estrogen and progesterone use for at least 5 years among women without hysterectomy (n = 23). Women with and without hysterectomy and no history of HRT use were selected for comparison (n = 46). Genome-wide methylation was measured in DNA from blood using the Illumina Infinium HumanMethylation450 BeadChip platform. After excluding loci on sex chromosomes, loci with detection p-values 1%, and loci with cross-reactive probes, 343,349 loci were included for analysis. Separately for the hysterectomy and non-hysterectomy groups, the M-value for each locus (defined as the logit of methylated probe intensity and overall intensity using a 0.001 threshold) was regressed against HRT status in linear models to adjust for age and BMI. The Significance Analysis of Microarrays (SAM) method was used to account for multiple comparisons by controlling the false discovery rate. Preliminary anal...

Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Jordahl, K. M., Doody, D. R., Zhang, Y., Yan, D., Randolph, T. W., Johnson, L. G., Li, C. I., Kelsey, K., Houseman, E. A., Wang, P., Malone, K. E., Bhatti, P. Tags: Epidemiology Source Type: research