Candidate Gene DNA Methylation Associations with Breast Cancer Characteristics and Tumor Progression

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::

• breast cancer
• breast cancer disparities
• DNA methylation
• estrogen/progesterone receptor
• GSTM2
• tumor progression

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2017-0119

Financial & competing interests disclosure

The Breast Cancer Care in Chicago study is supported by the NIH (NIH P50 2CA106743). J Kresovich received additional support from the National Cancer Institute Cancer Education and Career Development Program (NIH R25 CA057699). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The Breast Cancer Care in Chicago study is supported by the NIH (NIH P50 2CA106743). J Kresovich received additional support from the National Cancer Institute Cancer Education and Career Development Program (NIH R25 CA057699). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.