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Newly Identified Genetic Variations May Affect Breast Cancer Risk

Researchers have identified genetic variations in a region of DNA that may be associated with the risk for breast cancer. The finding is just the latest from a slew of ongoing genome-wide association studies funded by NIH.

Genome-wide association studies look across the entire genome for changes in the genetic code that are more frequent in people who have a certain disease than in similar people who don't. Researchers at NIH's National Cancer Institute (NCI) led a nation-wide research team in a 3-phase genome-wide association study into breast cancer. It was coordinated by researchers at Memorial Sloan-Kettering Cancer Center in New York, with participation from other centers in the United States, Canada and Israel.

Mutations in BRCA genes were identified in the 1990s as one of the strongest known genetic risk factors for breast cancer. In the current study, the researchers chose women who didn't carry the BRCA mutations so that they could uncover other influences. The researchers first analyzed more than 150,000 genetic variations in DNA samples from 249 Ashkenazi Jewish women who had breast cancer and a family history of the disease. The results were then compared to DNA samples from 299 Ashkenazi Jewish women who had not developed cancer. In the next 2 phases, the researchers verified their findings in over 2,000 more Ashkenazi Jewish women, about half with breast cancer and half without.

The team reported their results online in the Proceedings of the National Academy of Sciences on March 3, 2008. They found that 4 genetic variations located in a region of chromosome 6 were present more often in the breast cancer patients, suggesting that genes in this region might contribute to the risk of breast cancer. Variations in the region appeared to increase the risk of developing breast cancer by 1.4 times.

"We have already begun experiments to try to identify the genes associated with risk, and then try to characterize their function," said the study's lead author, Dr. Bert Gold of NCI's Center for Cancer Research. "It is hoped that identifying the genes responsible for this increased risk may lead to new therapies that target the actions of these genes."

The researchers also confirmed the finding of previous studies associating changes in the FGFR2 gene with a greater risk of breast cancer.

While the variations in chromosome 6 that increase breast cancer risk were found in 23% of the women studied, the increased risk of developing breast cancer that can be attributed to this new region is relatively small. The researchers estimate that only about 7% of breast cancer cases in this current study were associated with the region they located on chromosome 6. Interactions among multiple genes, however, may put a woman at greater risk of developing breast cancer.

“A better understanding of the genetic mutations that contribute to breast cancer is likely to come from the identification of these low-risk variants and from studies that investigate the mechanisms underlying their associations,” Gold explained.