Body Mass Index Is Associated with Gene Methylation in Estrogen Receptor-Positive Breast Tumors

Citation

Hair, Brionna Y.; Troester, Melissa A.; Edmiston, Sharon N.; Parrish, Eloise A.; Robinson, Whitney R.; Wu, Michael C.; Olshan, Andrew F.; Swift-Scanlan, Theresa; & Conway, Kathleen (2015). Body Mass Index Is Associated with Gene Methylation in Estrogen Receptor-Positive Breast Tumors. Cancer Epidemiology, Biomarkers & Prevention, 24(3), 580-586. PMCID: PMC4355173

Abstract

Background: Although obesity is associated with breast cancer incidence and prognosis, the underlying mechanisms are poorly understood. Identification of obesity-associated epigenetic changes in breast tissue may advance mechanistic understanding of breast cancer initiation and progression. The goal of this study, therefore, was to investigate associations between obesity and gene methylation in breast tumors.
Methods: Using the Illumina GoldenGate Cancer I Panel, we estimated the association between body mass index (BMI) and gene methylation in 345 breast tumor samples from Phase I of the Carolina Breast Cancer Study, a population based case-control study. Multivariable linear regression was used to identify sites that were differentially methylated by BMI. Stratification by tumor estrogen receptor status was also conducted.
Results: In the majority of the 935 probes analyzed (87%), the average beta value increased with obesity (BMI ≥ 30). Obesity was significantly associated with differential methylation (false discovery rate q-value < 0.05) in just 2 gene loci in breast tumor tissue overall and in 21 loci among estrogen receptor (ER)-positive tumors. Obesity was associated with methylation of genes that function in immune response, cell growth, and DNA repair.
Conclusions: Obesity is associated with altered methylation overall, and with hypermethylation among ER-positive tumors in particular, suggesting that obesity may influence the methylation of genes with known relevance to cancer. Some of these differences in methylation by obese status may influences levels of gene expression within breast cells. Impact: If our results are validated, obesity-associated methylation sites could serve as targets for prevention and treatment research.

URL

http://dx.doi.org/10.1158/1055-9965.epi-14-1017

Reference Type

Journal Article

Year Published

2015

Journal Title

Cancer Epidemiology, Biomarkers & Prevention

Author(s)

Hair, Brionna Y.
Troester, Melissa A.
Edmiston, Sharon N.
Parrish, Eloise A.
Robinson, Whitney R.
Wu, Michael C.
Olshan, Andrew F.
Swift-Scanlan, Theresa
Conway, Kathleen

PMCID

PMC4355173

ORCiD

Robinson, W - 0000-0003-4009-0488