AACR 2018: Researchers identify epigenetic changes that may help explain racial disparities in breast cancer

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As culture shapes our environment, which in turn influences how genes are expressed, cultural differences can have a profound effect on disease development.

For example, African-American mothers are less likely than mothers of European ancestry to breastfeed their children, and having given birth without breastfeeding is a known risk factor for aggressive breast cancer.

African-American women are more likely than women of African-American mothers to develop ER-negative breast cancer, a disease type in which tumours lack estrogen receptors, making them unresponsive to hormone therapy drugs and thus more difficult to treat.

Building upon previous research, Dr. Christine B. Ambrosone, PhD, Professor of Oncology, Senior Vice President of Population Sciences and Chair of Cancer Prevention & Control and colleagues suspected that epigenetic changes — or the switching on or off of genes in response to environmental influences such as diet, stress, physical activity, exposure to chemicals, or viral infections — were one force driving this disparity.

“Intergenic DNA methylation differences in ER- breast tumours from African American versus European American women”  is presented in a poster session today at the AACR Annual Meeting 2018, April 14-18, in Chicago.

DNA methylation is an epigenetic tool that cells may use to turn genes off.

For this study, the Roswell Park researchers focused on racial differences in DNA methylation within so-called non-coding or intergenic regions of the genome, which do not themselves encode genes, but often contain regulatory elements that influence gene expression.

Analysis of breast tumour samples from women of either African or European ancestry revealed higher DNA methylation levels at several genomic locations in tumours from African-American women.

These methylation patterns correlated with lower expression of key genes that promote the maturation of breast progenitor cells.

The authors speculate that incomplete maturation of progenitor cells, as a consequence of DNA methylation changes, may eventually translate into increased risk of ER-negative breast cancer.

“Our findings suggest that epigenetic differences between African-American women and women of European ancestry are important in breast cancer pathogenesis, and may underlie observed differences in the incidence of breast cancer subtypes by race,” says Dr. Matthew F. Buas, PhD, Assistant Professor of Oncology in the Department of Cancer Prevention and Control, and lead author.

“This research is exciting because it is helping us to understand, at the molecular level, what is driving ER-negative breast cancer in African-American women, which can lead to new approaches to prevention and treatment,” adds Dr. Ambrosone.


SourceRoswell Park Comprehensive Cancer Center

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