Candidate gene DNA methylation associations with breast cancer characteristics and tumor progression.

Abstract

We examined methylation patterns with aggressive tumor phenotypes and investigated demographic, socioeconomic and reproductive predictors of gene methylation. Pyrosequencing quantified methylation of BRCA1, EGFR, GSTM2, RASSF1, TFF1 and Sat 2. We used quantile regression models to calculate adjusted median methylation values by estrogen and progesterone receptor(ER/PR) status. Bivariate associations between participant characteristics and methylation were examined. Higher percent methylation of GSTM2 was observed in ER/PR-negative compared with ER/PR-positive tumors in ductal carcinoma in situ (14 vs 2%) and invasive (35 vs 3%) tissue components. Trends in aberrant GSTM2 methylation across tissue components were stronger among ER/PR-negative tumors (p-interaction<0.001). Black women were more likely to have ER/PR-negative tumors (p=0.01) and show hypermethylation of GSTM2 compared with other women (p=0.05). GSTM2 promoter hypermethylation may serve as a potential biomarker of aggressive tumor development and a mechanism for ER/PR-negative tumor progression.