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Mayo-led researchers discover genetic variants modifying breast cancer risk
Date:9/19/2010

ROCHESTER, Minn. -- Individuals with disrupting mutations in the BRCA1 gene are known to be at substantially increased risk of breast cancer throughout their lives. Now, discoveries from an international research team led by Mayo Clinic researchers show that some of those persons may possess additional genetic variants that modify their risk. These new findings enhancing individualized medicine appear in the current Nature Genetics.

"These findings should be useful in helping determine individual risk for breast cancer in BRCA1 carriers," says Fergus Couch, Ph.D., Mayo investigator and senior author of the study. "It also provides insights into hormone-receptor-negative breast cancer in the general population."

Genetic mutations in the BRCA1 gene give carriers of these mutations an increased risk for developing breast cancer. To determine if any genetic variations would modify or alter this risk among large populations of the mutation carriers, the researchers conducted genome-wide association studies (GWAS) that ultimately spanned 20 research centers in 11 different countries.

They first studied 550,000 genetic alterations from across the human genome in 1,193 carriers of BRCA1 mutations under age 40 who had invasive breast cancer and compared the alterations to those in 1,190 BRCA1 carriers of similar age without breast cancer. The 96 single nucleotide polymorphisms (SNPs) discovered were subsequently studied in a larger sample population of roughly 3,000 BRCA1 carriers with breast cancer and 3,000 carriers without cancer. Researchers found five SNPs associated with breast cancer risk in a region of chromosome 19p13.

Further studies of those SNPs in 6,800 breast cancer patients without BRCA1 mutations showed associations with estrogen-receptor-negative disease, meaning cancer in which tumors don't possess estrogen receptors. In another GWAS involving 2,300 patients, the five SNPs also were associated with triple-nega
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Contact: Robert Nellis
newsbureau@mayo.edu
507-284-5005
Mayo Clinic
Source:Eurekalert

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