NEW YORK (Reuters Health) – Epigenetic changes may help explain racial disparities in estrogen receptor (ER)-negative breast cancer, say researchers from Roswell Park Comprehensive Cancer Center in Buffalo, New York.
“African-American women are more likely than white women to be diagnosed with aggressive breast cancers that do not express the estrogen receptor (ER-negative), thus with fewer targets for therapy and treatment, and with poorer prognosis,” senior author Dr. Christine Ambrosone told Reuters Health by email.
Based on earlier research, Dr. Ambrosone and colleagues suspected that epigenetic changes – the turning on or off of genes in response to environmental influences such as diet, stress, physical activity, exposure to chemicals, or viral infections – may drive this disparity.
In a prior study, the Roswell Park team performed genome-wide DNA methylation profiling of 224 tumor samples from 141 African-American and 83 European-American women.
“The goal of the study was to see if there were more genes that were ‘turned off’ through DNA methylation, which results in lower gene expression. In that first study, we found differences in methylation between whites and blacks and between ER-positive and ER-negative tumors when looking at promoter regions within genes,” Dr. Ambrosone explained.
In their latest study, they focused on ER-negative tumors to see if there were racial differences in methylation in areas between genes, so-called intergenic areas, and to identify if there were genes farther away whose expression was affected by this methylation.
“Results from this study showed that there were, indeed, higher levels of methylation in several of these non-coding areas, and that it affected the expression levels of genes that were located farther away from those areas,” Dr. Ambrosone said.
“One area that was less methylated in African Americans is predicted to interact with a gene that is a pro-tumorigenic cancer-testis antigen; other areas that were more methylated in blacks appear to affect genes that promote maturation of breast cells,” she added. It’s possible that incomplete maturation of progenitor cells, as a consequence of DNA-methylation changes, may eventually translate into increased risk of ER-negative breast cancer.
The researchers reported their findings in a poster April 18 at the American Association for Cancer Research (AACR) annual meeting in Chicago.
“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,” lead author Dr. Matthew Buas said in a statement.
“These results are not readily translatable to the clinic yet,” Dr. Ambrosone told Reuters Health. “However, they do help us to better understand the importance of areas between genes that had been thought to have no function and that these ‘intergenic’ areas may be a key to understanding how cancer develops. It may also help to provide new targets for therapy.”
“Next steps will be to dive more deeply into studying which genes are greatly affected by methylation in these intergenic regions, which we are in the process of doing, and conducting laboratory studies to determine how these processes occur,” said Dr. Ambrosone. “This will guide us to better understand what is driving the occurrence of ER-negative breast cancer in African-American women, particularly conducting larger studies so that we can examine if specific risk factors that are more common in black women, such as having children and not breastfeeding, are associated with methylation in these areas.”
SOURCE: https://bit.ly/2K0dRCN
American Association for Cancer Research 2018.
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