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A mutation in the CHEK2 gene, which encodes a protein involved in preventing division of cells that have damaged DNA, may be implicated in increased susceptibility to breast cancer in individuals who do not carry a mutation in either the BRCA1 or BRCA2 gene [The CHEK2-Breast Cancer Consortium (2002), advance on-line publication in Nature Genetics]. The CHEK2 mutation was found in 1.1% of control individuals in populations from Europe and North America but in 5.1% of patients from breast cancer families who were negative for BRCA1 and BRCA2 mutations (p=0.00000003). The frequency of the mutation in patients from breast cancer families who carried BRCA1 or BRCA2 mutations was the same as in controls. The penetrance of the CHEK2 mutation appears to be low, conferring approximately a two-fold increase in risk of breast cancer in women, and a ten-fold increased risk in men. Several different genetic variants have been proposed as low-penetrance susceptibility alleles for breast cancer, but the CHEK2 consortium claims that this is the first to show such high statistical significance.

Comment: It is difficult to predict the eventual clinical significance of this work, as it is uncertain whether genetic testing for a variant conferring a relative risk of two would be seen as worthwhile, or what intervention should be offered to individuals carrying the mutation. The findings also need independent confirmation from other research groups.