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Geneticists identify four new breast-cancer genes

May 27, 2007 By John Whitfield This article courtesy of Nature News.

Discovery adds to understanding of individuals' susceptibility.

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A large-scale genetic study has identified four new genes that significantly affect a woman's risk of developing breast cancer.

The finding could allow doctors to predict cancer risk more accurately, and to guide treatments to prevent and cure the disease. But more important is what it might tell researchers about how the disease works, says Douglas Easton of the University of Cambridge, a member of the team that made the discovery. "We had no inkling that these genes had anything to do with breast cancer," he says.

Breast cancer — which will affect about one in every nine women in Britain and the United States — is known to have a strong genetic influence. But until now, known genes could account for only about a quarter of the genetic component of cancer risk.

As more genes are identified, tests will become more predictive.
Douglas Easton, University of Cambridge
To search for some of the many other genes thought to make small differences to a woman's breast-cancer risk, Easton and his colleagues compared the genomes of some 4,400 women with breast cancer with those of about 4,300 who did not have the disease.

They identified 30 differences in single DNA bases that seemed to be linked to the disease. These were then compared in more than 20,000 women with breast cancer and in a similar number of controls. The results are reported in Nature1.

Growing pains

Three of the newly discovered genes are involved in controlling the growth of cells. The gene with the strongest association was fibroblast growth factor receptor 2, or FGFR2.

Women who have two copies of the high-risk version of this gene — about 16% of the population — have a 60% greater chance of developing breast cancer than do those with no copies of the gene, Easton and his colleagues found.

At present, scanning these newly discovered genes would tell us little about a woman's cancer risk. But as more and more genetic risk factors are uncovered, genetic profiling could give doctors a fine-grained picture of individual risk, and could even lead to bespoke treatments offering the best chance of preventing or treating the disease.

"As more genes are identified, tests will become more predictive," says Easton. "I wouldn't be at all surprised if there were dozens or hundred of genes involved." A similar approach ought to work for other diseases — Easton is now studying prostate cancer.

Two further studies also identify further genetic variants associated with an increased risk of breast cancer. One3, looking at about 2,000 postmenopausal women and a similar number of controls, also identified genetic variants in the FGFR2 gene associated with increased cancer risk2. And in the other3, researchers studying Icelandic women found mutations on chromosomes 2 and 16 that seem to heighten the risk of cancer.

References

  1. Easton D. F., et al. Nature, doi:10.1038/nature05887 (2007).
  2. Hunter D. J., et al. Nature Genet. , doi:10.1038/ng2075 (2007).
  3. Stacey S. N., et al. Nature Genet., 10.1038/ng2064 (2007).

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