Scientists Identify Five New Genetic Loci Linked with Increased Risk of Breast Cancer

Five new genetic regions have been identified that appear to increase the risk of developing breast cancer by 6–16%, according to researchers from the Institute of Cancer Research. The results, from what they claim is the largest genome-wide analysis of breast cancer patients to date, suggest that most of the new regions predispose predominantly toward estrogen receptor-positive breast cancers. The team says that this observation could lead to new avenues of research for the use of drugs such as tamoxifen.

The study is published in Nature Genetics in a paper titled “Genome-wide association study identifies five new breast cancer susceptibility loci.” The first stage of the genome-wide association study involved genotyping 582,886 SNPs in 3,659 cases of breast cancer with a family history of the disease and 4,897 controls. Promising genetic associations were then evaluated in a second stage that involved 12,576 cases and 12,223 controls.

The results generated five new susceptibility loci on chromosomes 9, 10, and 11. The study also suggested that SNPs in the 6q25.1 and LSP1 regions had a more significant association with risk than had previously been reported. The authors, led by professor Doug Easton, M.D., director of Cancer Research UK’s genetic epidemiology unit at the University of Cambridge, say the findings mean that a total of 18 common, low-risk genetic sites have now been linked with an increased risk of breast cancer.

“The newly identified loci explain approximately 1.2% of the familial risk of breast cancer, though the overall contribution may be larger because the true causal variants may be more strongly associated with disease than the SNPs tagging them in this study,” they report. “Taken together with estimates from previous studies, the 18 confirmed breast cancer susceptibility loci explain approximately 8% of the familial risk of breast cancer, whereas rarer mutations in the known high-risk loci [principally BRCA1 and BRCA2] and moderate-risk loci explain about a further 20%.”

Although one of the newly identified loci contains CDK2NA, a gene that has also been linked to melanoma, the authors stress that more work will be needed to definitively pinpoint which genes are causing the increased breast cancer risk. They also suggest that identifying even more genetic loci will help both with the search for new treatments and with more accurate predictive tests.

“While each of these sites has a small impact on breast cancer risk, by finding more of these genes we may be able to develop a test that can predict more reliably a woman’s risk of developing breast cancer,” Dr. Easton concludes. The work was funded by Cancer Research UK and the Wellcome Trust.