Women with BRCA1 mutations may possess additional genetic variants that affect their risk for breast cancer

Antoniou AC. Nat Genet. 2010; doi:10.1038/ng.669.

Identifying genetic variations in women with BRCA1 mutations may help in understanding the mechanisms behind the development of breast cancer, according to researchers. Additionally, it may help to identify certain women with BRCA1 who are at lower risk for cancer, and help those at high risk to make decisions about changing their approach to cancer prevention.

“These findings should be useful in helping determine individual risk for breast cancer in BRCA1 carriers,” Fergus J. Couch, PhD, professor in the department of laboratory medicine and pathology at the Mayo Clinic in Rochester, Minn., said in a press release. “It also provides insights into hormone receptor-negative breast cancer in the general population.”

The team, led by researchers from the Mayo Clinic, performed a study to determine whether genetic variations would modify risk among large populations of carriers of the mutation. They conducted genome-wide association studies that included 20 research centers in 11 countries.

They examined 550,000 genetic alterations from across the human genome in 1,193 women aged younger than 40 years with BRCA1 mutations who had invasive breast cancer and compared those gene alterations to that of 1,190 women with BRCA1 mutations without breast cancer.

They identified 96 single nucleotide polymorphisms and assessed them in a larger sample population of about 3,000 BRCA1 carriers with breast cancer and 3,000 carriers without cancer. Five SNPs were associated with breast cancer risk in a region of chromosome 19p13.

Further examination of those SNPs in 6,800 patients with breast cancer without BRCA1 mutations showed associations with ER-negative disease. In another genome-wide association study involving 2,300 patients, the five SNPs were associated with triple-negative breast cancer.

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