Breast Cancer Risk in CHEK

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Science  03 May 2002:
Vol. 296, Issue 5569, pp. 807
DOI: 10.1126/science.296.5569.807d

Women with mutations in the BRCA1 or BRCA2 genes have a high risk of developing breast cancer; however, only 15 to 20% of overall familial risk for the disease can be explained by the presence of these two genes. According to current models, the residual familial clustering is unlikely to be due to rare mutations in additional high-risk genes but is more likely to be due to common variants of a large number of genes, each of which confers a small effect on disease risk.

A large Breast Cancer Consortium has now identified the CHEK2 gene on chromosome 22q as one of these so-called “low-penetrance” breast cancer susceptibility genes. CHEK2 encodes a cell-cycle checkpoint kinase that is activated in response to DNA damage and prevents the cell from entering mitosis. A truncating variant allele of CHEK2 that abolishes the protein's kinase activity was found to confer a twofold increase in the risk of breast cancer risk for women and a 10-fold increase in risk for men.—PAK

Nature Genet. 10.1038/ng879 (2002).

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