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Analysis of key breast cancer genes reveals distinct profiles for African-American, European-American women

Date:
January 29, 2015
Source:
Roswell Park Cancer Institute
Summary:
Epidemiologists have determined that gene variations associated with breast cancer risk diverged significantly between African-American and women of European descent, a large study shows.
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Researchers 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, which strengthens the evidence that increased dietary folate intake may prove to be an effective strategy for reducing risk for the disease in African-American women. In the first large study of its kind, the team, led by Roswell Park Cancer Institute (RPCI) epidemiologists Zhihong Gong, PhD, and Christine Ambrosone, PhD, identified patterns in gene variations associated with breast cancer risk that diverged significantly between African-American women and women of European descent.

The researchers, who included collaborators from the Rutgers Cancer Institute of New Jersey and the Icahn School of Medicine at Mount Sinai School of Medicine, 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.

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, a multisite study designed to evaluate risk factors for early and aggressive forms of breast cancer, they conducted a comprehensive analysis of single-nucleotide polymorphisms (SNPs) 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 SNPs -- particularly in genes such as MTR, MTRR, SHMT1, TYMS, and SLC19A1 -- with overall breast cancer risk and with breast cancer risk by estrogen-receptor (ER) status. While the single-SNP 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 SNP associations may be modified by level of dietary intake of folate, a B vitamin found in leafy green vegetables and fruits. And 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.

"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 Dr. Gong, 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 SNPs to shed additional light on differences in association by race and uncover potential associations with breast cancer outcomes.

The study, "Genetic variants in one-carbon metabolism genes and breast cancer risk in European American (EA) and African American (AA) women," has been published online ahead of print in the International Journal of Cancer.


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Materials provided by Roswell Park Cancer Institute. Note: Content may be edited for style and length.


Journal Reference:

  1. Zhihong Gong, Song Yao, Gary Zirpoli, Ting-Yuan David Cheng, Michelle Roberts, Thaer Khoury, Gregory Ciupak, Warren Davis, Karen Pawlish, Lina Jandorf, Dana H. Bovbjerg, Elisa V. Bandera, Christine B. Ambrosone. Genetic variants in one-carbon metabolism genes and breast cancer risk in European American and African American women. International Journal of Cancer, 2015; DOI: 10.1002/ijc.29434

Cite This Page:

Roswell Park Cancer Institute. "Analysis of key breast cancer genes reveals distinct profiles for African-American, European-American women." ScienceDaily. ScienceDaily, 29 January 2015. <www.sciencedaily.com/releases/2015/01/150129093857.htm>.
Roswell Park Cancer Institute. (2015, January 29). Analysis of key breast cancer genes reveals distinct profiles for African-American, European-American women. ScienceDaily. Retrieved March 18, 2024 from www.sciencedaily.com/releases/2015/01/150129093857.htm
Roswell Park Cancer Institute. "Analysis of key breast cancer genes reveals distinct profiles for African-American, European-American women." ScienceDaily. www.sciencedaily.com/releases/2015/01/150129093857.htm (accessed March 18, 2024).

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