Breast Cancer Genetics Takes Big Leap Forward

"Then the question is, well, maybe it's a conglomeration of things, and what does that complex conglomeration look like?" Chanock continued. "We are just at the dawn of pulling out the major pieces of that."

The first study, appearing inNature, involved several stages of analysis. That, in turn, led to an analysis of 30 single nucleotide polymorphisms ("SNPs") in 21,860 breast cancer patients and 22,578 controls.

Out of that analysis, the investigators, based in Cambridge, U.K., identified four genes linked with genetic susceptibility to breast cancer (FGFR2,TNRC9,MAP3K1andLSP1).

The researchers also found five regions of DNA that were present more often in breast cancer patients, suggesting that elements in these regions might raise a woman's risk.

A second study, this one appearing inNature Genetics, was carried out as part of a collaboration -- called The Cancer Genetic Markers of Susceptibility or CGEMS project -- between Harvard and the NCI. It found that variations of the geneFGFR2were associated with a heightened risk of breast cancer.

Women of European ancestry who inherited one copy of theFGFR2mutation increased their breast cancer risk by about 20 percent and by 60 percent if they had two copies.

This same association was found by the Cambridge researchers as well.

TheseFGFR2variants, which appear to be involved in cell growth or division, are thought to be present in more than 60 percent of U.S. female adults.

The final paper, also appearing inNature Genetics, found genetic variants on chromosome 2 and on chromosome 16 that increase the risk of estrogen-receptor-positive breast cancer. One of these variants is located nearTNRC9, which was identified in the U.K. study.

Researchers are not advocating that each gene be tested, because the risk from each is relatively small. One day, however, a test for gene combinations may be useful.

"We wouldn't ask to test each of them but, certainly, as we learn more about this, it will give us more clues about the etiology and biology and may lead to differences in treatment," Feigelson said. "This tells us what genes and where to look, and that's the important first step."

"These are all markers. They don't tell you why someone gets breast cancer. They tell us that parts of the genome are very, very important," Chanock added. "We have to figure out what they are."

The technology used in the research only became available last year and is now being applied to a wide variety of diseases, including diabetes and prostate cancer. It will also continue to be applied to the genetics of breast cancer.

"This is sort of the middle of the story," Hunter said. "It is by no means the end of the story."

More information

Visit the U.S. National Cancer Institute for more on its Cancer Genetic Markers of Susceptibility project.

SOURCES: Heather Spencer Feigelson, Ph.D., strategic director, genetic epidemiology, American Cancer Society, Atlanta; Stephen Chanock, M.D., senior investigator, National Cancer Institute; David J. Hunter, Sc.D., professor, cancer prevention, Harvard School of Public Health, and epidemiologist, Brigham & Women's Hospital, Boston; May 27, 2007,Nature,Nature Genetics