Researchers discover genetic variants modifying breast cancer risk

September 19, 2010

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 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."

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 from across the human genome in 1,193 carriers of BRCA1 mutations under age 40 who had 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-negative breast cancer, an aggressive form of the disease accounting for about 12 percent of all breast cancer. Triple-negative tumors don't express genes for estrogen or progesterone receptors or Her2/neu. The researchers also found that these SNPs were not related to risk for ovarian cancer in BRCA1 mutations carriers.

By locating these risk-modifying SNPs, the researchers have provided a target for better understanding the mechanisms behind the development of breast cancer. Furthermore, when combined with other risk-modifying SNPs that remain to be identified in ongoing studies by this group, it may be possible to identify certain BRCA1 carriers who are at lower risk of cancer and, also, carriers at particularly elevated risk of cancer who may decide to change their approach to cancer prevention.

Explore further: Ashkenazi ovarian cancer patients with BRCA mutations live longer than those with normal gene

More information: Paper online:

Related Stories

BRCA1 mutation linked to breast cancer stem cells

January 31, 2008

A new study may explain why women with a mutation in the BRCA1 gene face up to an 85 percent lifetime risk of breast cancer. Researchers from the University of Michigan Comprehensive Cancer Center found that BRCA1 plays a ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.