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Women with mutations in a gene called BRIP1 have twice the normal risk of breast cancer, according to a study to be published in the November 2006 issue of Nature Genetics.
Mutations in three genes - BRCA1, BRCA2, and TP53 - are known to greatly increase the chance of developing breast cancer over a lifetime: for example, women carrying a BRCA mutation have a 50-80% chance of developing the disease. Mutations in two other genes - CHEK2 and ATM - confer a much more modest risk. Nazneen Rahman and colleagues screened 1,212 women with breast cancer, who did not have mutations in BRCA1 and BRCA2, for mutations in BRIP1. They report that nine of these women had mutations in the BRIP1 gene, which most likely inactivates the BRIP1 protein; only two of 2,081 women in a 'control' group without breast cancer demonstrated such mutations. The authors estimate - by taking into consideration information from the control group and the families of affected individuals - that BRIP1 mutations result in an approximately two-fold increase in the risk of breast cancer, which puts the gene into the same class as CHEK2 and ATM. They believe that mutations in these so-called 'low-penetrance' susceptibility genes likely only predispose to cancer in concert with other mutations and/or environmental factors, and account for only a small fraction of the familial risk of breast cancer. Like the other risk genes, BRIP1 is involved in DNA repair, lending support to the idea that unrepaired DNA damage is a key trigger for breast cancer development. Author contact: Nazneen Rahman (Institute of Cancer Research, Sutton, UK)
E-mail: nazneen.rahman@icr.ac.uk Abstract available online.
(C) Nature Genetics press release.
Message posted by: Trevor M. D'Souza
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