Four New Breast Cancer Genes Discovered

A large-scale genetic study involving scientists from 15 countries has found four new genes that appear considerably to raise a woman's risk of getting breast cancer.

The four genes are called FGFR2, TNRC9, MAP3K1, and LSP1. The study published in the May 27, 2007 early online edition of the journal Nature, was conducted by scientists from Australia, Denmark, Finland, France, Germany, Korea, The Netherlands, New Zealand, Poland, Singapore, Sweden, Taiwan, Thailand, the United Kingdom, and the United States.

According to Dr. Douglas Easton, from the University of Cambridge (UK), who was involved in the research, this discovery could help physicians improve their prediction of breast cancer risk and choose better treatments to prevent and cure the disease. But more significantly is how these findings help researchers find out how the disease works. "We had no inkling that these genes had anything to do with breast cancer,” said Dr. Easton.

More than 10% of women in the United States and the United Kingdom are affected by breast cancer, which is believed to have a significant genetic component. But until this new study, scientists could only account for about 25% of the genetic part of breast cancer risk. They suspected that the residual genetic variance was probably due to a variety of different gene mutations.

To look for further mutations that might be associated with breast cancer, Dr. Easton and colleagues conducted a two-stage Genome-Wide Association Study (GWAS) in nearly 4,400 women with breast cancer and a similar number of control subjects. They then confirmed 30 suspected single nucleotide polymorphisms (SNPs) in about 22,000 women with breast cancer and a similar number of controls spanning 22 studies.

Overall, the researchers looked at over 225,000 SNPs and discovered that five until now unknown loci in the genome demonstrated strong and consistent links with breast cancer incidence. Four of these were found to be the most plausible: FGFR2, TNRC9, MAP3K1, and LSP1. However, they reported that there might well be many other mutations that contribute to a higher risk of breast cancer that could be found using their approach.

The gene whose variants appear to present the greatest risk of the four is fibroblast growth factor receptor 2 (FGFR2). Women who have two copies of the high-risk variants of this gene, estimated to be about 16% of the female population, have a 60% greater risk of getting breast cancer compared with women who have none, according to Dr. Easton and colleagues.

These findings alone are not enough to enable clinicians to scan a woman's genes and inform her what is likely to be her breast cancer risk. But, as more of these studies are performed and more risk factors revealed, the more realistic such a scenario becomes. "As more genes are identified, tests will become more predictive,” said Dr. Easton. "I wouldn't be at all surprised if there were dozens or hundred of genes involved.”

Dr. Easton believes a similar approach will work for other cancers, and he is now evaluating prostate cancer. Two other studies published in the May 27, 2007, issue of the journal Nature Genetics have also discovered genetic variants that appear to increase the risk of breast cancer.

One study conducted in the United States and led by Dr. David J. Hunter, from the department of medicine, Brigham and Women's Hospital and Harvard Medical School (Boston, MA, USA), is also a Genome-Wide Association Study. This GWAS evaluated about 2,000 postmenopausal women and 2,000 control subjects, and found several genetic variants in the FGFR2 gene associated with increased risk of breast cancer.

In the other study, led by Dr. Simon N. Stacey from deCODE genetics (Reykjavik, Iceland), an international team of scientists found mutations on chromosomes 2 and 16, which appear to increase the risk of estrogen receptor-positive breast cancer. Overall, they studied over 4,500 affected Icelandic women and 17,000 controls.


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