Get them CHEKed out

CHEK2 gene implicated in breast cancer risk along
with BRCA1 and 2

By Owen Dyer

Villains usually come in duos � Bonny and Clyde, Butch Cassidy and the Sundance Kid, Bush and Cheney. The same goes for the notorious breast cancer genes BRCA1 and 2, right? Unfortunately, that's no longer true 'cause this duo just got a third partner in crime. A study published in the June issue of the American Journal of Human Genetics suggested that a faulty copy of the CHEK2 gene doubles the risk of developing breast cancer. The research brings us closer to developing a comprehensive genetic test for breast cancer risk, but the authors believed there are still more genetic criminals that have yet to be caught.

CHEK2 has been suspected of a role in carcinogenesis fora while. The study, led by Cancer Research UK's Genetic Epidemiology Unit at the University of Cambridge, tested 10,860 breast cancer patients and 9,065 healthy women in the UK, Australia, Finland, Germany and the Netherlands for faulty versions of the gene. The variant CHEK2 gene was found in 201 of the cancer patients, but only in 64 of the healthy controls. This suggested that the faulty gene elevates risk by a factor of slightly more than two. Unlike the BRCA genes, however, CHEK2 appears to be concentrated in younger patients.

CHEK2 also contrasts with the BRCA genes in that its effect seems to be independent of family history of the disease. Patients who carry faulty BRCA genes are only deemed at increased breast cancer risk if they have a family history.

This complicates identifying patients who would benefit from genetic screening in the case of CHEK2. Dr Doug Easton, who led the research, said: "Women with a strong family history of breast cancer can already receive genetic tests for the BRCA genes. As we identify more genes that impact on hereditary breast cancer, we move closer to a comprehensive genetic test to accurately assess the risk of inheriting the disease." However, with CHEK2 there's no rationale for concentrating screening in a population, and a screening program for all women is not exactly cost-effective.

Faulty versions of CHEK2 are also rarer than faulty BRCA genes. While the BRCA variants are implicated in about 10% of breast cancers, the proportion of cases attributable to CHEK2 would be nearer to 1%. The researchers believed, however, that other low-risk genes exist and that if more could be identified, a single genetic test could eventually help paint a fairly accurate picture of a patient's breast cancer risk.

Professor Robert Souhami, director of Clinical and External Affairs at Cancer Research UK, said: "Identifying the first of a new set of breast cancer genes puts us in a much better position to tackle breast cancer, both through testing high-risk groups and eventually through new clinical strategies."