DNA Methylation and Differential Cancer Aggressiveness by Race or Ethnicity

Abstract

African American breast cancer patients are more likely than their white counterparts to be diagnosed with late stage, high grade disease and aggressive subtypes of breast cancer. DNA methylation helps to maintain tissue-specific patterns of gene expression; aberrant methylation of gene promoters can silence tumor suppressor genes while their hypomethylation may reactivate proto-oncogenes. DNA methylation also stabilizes interspersed and tandem repeats, and hypomethylation of these repeats is common in breast cancer.

Few studies have examined DNA methylation as a possible contributor to disparities in breast cancer aggressiveness. We hypothesize that the greater tendency for more aggressive breast cancer in African American and Hispanic patients compared to Whites is due in part to greater DNA methylation aberration in African American and Hispanic patients. We will analyze paired samples of invasive and adjacent normal tissues from 365 patients with breast cancer and breast samples from 150 unaffected women. Histologic grade will be determined by centralized pathology review, and breast cancer subtypes will be based on immunohistochemistry analyses. Using pyrosequencing we will quantitate DNA methylation for the interspersed repeat LlNE-1 and the pericentromeric tandem repeat satellite 2.

We will analyze gene promoter methylation across 807 genes by a high-throughput bisulfite- and ligation-based assay (Illumina GoldenGate) and we will quantitate BRCA1 promoter methylation and BRCA1 protein by immunohistochemistry. Additional immunohistochemical markers will be chosen to follow-up on interesting findings once the majority of methylation results have been obtained.

We also propose to examine associations between potential markers of stress and aberrant DNA methylation, and to lay the ground work for a cohort study of biological stress, DNA methylation and breast cancer in high-risk minority women. Environmental exposures and social contexts could act through DNA methylation to infiuence breast cancer aggressiveness. While the proposed study is mainly correlational in nature, results will provide insight regarding the contribution of aberrant DNA methylation to breast cancer aggressiveness and disparities.

Research Partner(s)

University of Chicago
Rush University

Affiliated Center/Program

Funding Agency
Start date
07/01/2010
End date
06/30/2016
About this grant

This is a project within a center grant, the Center for Population Health and Health Disparities.

Related publications


Rauscher GH, Campbell RT, Wiley EL, Hoskins K, Stolley MR, Warnecke RB. Mediation of racial and ethnic disparities in estrogen/progesterone receptor-negative breast cancer by socioeconomic position and reproductive factors. Am J Epidemiol. 2016 May 15;183(10):884-93. [See abstract.]

Benevolenskaya EV, Islam AB, Ahsan H, Kibriya MG, Jasmine F, Wolff B, Al-Alem U, Wiley E, Kajdacsy-Balla A, Macias V, Rauscher GH. DNA methylation and hormone receptor status in breast cancer. Clin Epigenetics. 2016 Feb 16;8:17. [See abstract.]

Rauscher GH, Kresovich JK, Poulin M, Yan L, Macias V, Mahmoud AM, Al-Alem U, Kajdacsy-Balla A, Wiley EL, Tonetti D, Ehrlich M. Exploring DNA methylation changes in promoter, intragenic, and intergenic regions as early and late events in breast cancer formation. BMC Cancer. 2015 Oct 29;15:816. [See abstract.]