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

Epigenomics. 2018 Apr 1;10(4):367-378. doi: 10.2217/epi-2017-0119. Epub 2018 Mar 12.

Abstract

Aim: We examined methylation patterns with aggressive tumor phenotypes and investigated demographic, socioeconomic and reproductive predictors of gene methylation.

Materials & methods: 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.

Results: 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).

Conclusion: GSTM2 promoter hypermethylation may serve as a potential biomarker of aggressive tumor development and a mechanism for ER/PR-negative tumor progression.

Keywords: DNA methylation; GSTM2; breast cancer; breast cancer disparities; estrogen/progesterone receptor; tumor progression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / genetics*
  • DNA Methylation*
  • Disease Progression
  • Female
  • Glutathione Transferase / genetics
  • Humans
  • Middle Aged
  • Promoter Regions, Genetic
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone
  • Glutathione Transferase
  • glutathione S-transferase Mu 2