Researchers have identified common genetic variations associated with breast cancer in several populations of women. The variants occur in a tumor suppressor gene called FGFR2 (Fibroblast Growth Factor Receptor 2), which was previously reported to be amplified or overexpressed in some breast cancers.

Two independent research teams - one in the U.S. and one in the U.K. - made the discovery by conducting genome-wide association studies to look for breast cancer susceptibility genes. They scanned DNA from thousands of women with breast cancer and from healthy women. In both studies, variants in FGFR2 were linked to disease risk.

"This gene is a substantial new risk factor for breast cancer," says Dr. David Hunter of the Harvard School of Public Health and NCI, and lead author of the U.S. study. "The discovery opens up new avenues for research on the gene and its signaling pathway, which may have relevance to treatment and prevention."

For women of European descent, a single copy of the variant gene increases breast cancer risk by 20 percent while two copies increase risk by 60 percent, or about the same amount as having a single family member with the disease. Approximately 15 percent of white women are estimated to carry two copies of the variant gene.

Dr. Hunter says that it would be premature to test women for the FGFR2 risk variants. Additional variants are likely to be found as the researchers analyze the genome data generated as part of the study, conducted under NCI's Cancer Genetic Markers of Susceptibility (CGEMS) program.

In the study's next phase, CGEMS researchers are evaluating 29,000 variants linked to breast cancer risk during a series of collaborative studies, mostly drawn from the NCI Breast & Prostate Cancer Cohort Consortium. The aim is to build a catalogue of genetic risk factors that can be evaluated along with environmental factors, such as hormone use.

The findings appeared online in Nature Genetics on May 27. The same day, the U.K. group, which included researchers from NCI's Division of Cancer Epidemiology and Genetics (DCEG), published findings online in Nature. Dr. Douglas Easton of Cancer Research UK at the University of Cambridge and his colleagues identified FGFR2 and three other novel breast cancer susceptibility genes (TNRC9, MAP3K1, and LSP1).

The function of these genes in breast cancer susceptibility is not known. Taken together, the new findings provide leads for identifying new biological processes in breast cancer and may contribute to the familial risk not explained by BRCA mutations.