Analysis of Key Breast Cancer Genes Reveals Distinct Profiles for African American, European American Women
Researchers at Roswell Park Cancer Institute (RPCI) have uncovered new information that may begin to explain why many African American women are more likely to be diagnosed with aggressive, often deadly forms of breast cancer. Their findings also strengthen evidence that increased dietary folate intake may prove to be an effective strategy in reducing risk for the disease in African American women. Their findings have been published by Gong et al in the International Journal of Cancer.
In the first large study of its kind, researchers identified patterns in gene variations associated with breast cancer risk that diverged significantly between African American and European American women. The researchers, including collaborators from the Rutgers Cancer Institute of New Jersey and the Icahn School of Medicine at Mount Sinai, honed in on differences in folate-regulated one-carbon metabolism, a complex network of interdependent processes that enable key cell processes such as DNA methylation, nucleotide synthesis, and DNA replication and repair.
Study Details
In a case-control study involving 1,275 European American and 1,299 African American women who participated in the Women’s Circle of Health Study, researchers conducted a comprehensive analysis of single-nucleotide polymorphisms in 11 genes involved in one-carbon metabolism and risk of breast cancer.
They found distinct patterns in these genetic variations between the two groups of women and identified associations between several of those single-nucleotide polymorphisms—particularly in genes such as MTR, MTRR, SHMT1, TYMS, and SLC19A1—with overall breast cancer risk and with breast cancer risk by estrogen receptor status. While the single-nucleotide polymorphism associations they uncovered were not statistically significant after adjustment for key factors, their polygenetic risk-score analyses revealed significant associations between the variations and breast cancer risk.
Importantly, the findings also indicate that single-nucleotide polymorphism associations may be modified by level of dietary intake of folate, a B vitamin found in leafy green vegetables and fruits. The team’s investigations of genes that have not previously been well studied in breast cancer led to new findings about the metabolism of key enzymes.
‘Provocative’ Findings
“These findings are provocative because they provide new evidence that by disrupting key processes and ultimately contributing to gene instability, certain genetic variants and interactions in these key metabolic pathways may contribute to risk of breast cancer in both African American and European American women,” says Zhihong Gong, PhD, Assistant Professor of Oncology and Assistant Member of the Department of Cancer Prevention and Control at RPCI.
Additional large-scale studies and functional evaluations will be needed, the authors note, to confirm these findings and explore the molecular mechanisms responsible for these dynamics. The researchers plan to further investigate associations of blood folate levels, dietary folate intake, and genotypes of these key single-nucleotide polymorphisms to shed additional light on differences in association by race, and uncover potential associations with breast cancer outcomes.
Dr. Gong is the corresponding author for the International Journal of Cancer article.
This study was supported by the U.S. Army Medical Research and Material Command, the National Cancer Institute, the Breast Cancer Research Foundation, and by a gift from the Philip L. Hubbell family.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
