Risk Factor: Genetic defect hikes breast cancer threat

A mutation already linked to several types of cancer doubles the risk of breast cancer in a woman and multiplies men’s slight risk even more dramatically, a new study finds.

The protein encoded by the normal version of the gene called CHEK2 or CHK2 signals a cell to stop dividing if its DNA is damaged, says study coauthor Douglas F. Easton, a genetic epidemiologist at Cambridge University in England.

The protein appears to activate the proteins encoded by cancer-fighting genes BRCA1 and p53, says cancer geneticist Daniel A. Haber of the Massachusetts General Hospital Cancer Center in Charlestown, Mass. The full picture of how these genes and their proteins work is far from clear, he says. Nevertheless, he calls the study “fascinating and unexpected.” Haber and his colleagues had earlier implicated a CHEK2 mutation in a syndrome that includes breast cancer, brain cancer, and sarcoma, a cancer of connective tissues.

A mutation in BRCA1 imparts more-serious risk than a defective CHEK2 does, Easton says. Studies have shown that a woman with a mutation in BRCA1 faces a 60 percent or higher lifetime risk of getting breast cancer. A woman with a CHEK2 mutation faces a doubling of the standard lifetime breast cancer risk, Easton says, which is roughly 13 percent in the United States.

Only about 1 percent of breast cancers occurs in men. However, having a mutated CHEK2 hikes men’s risk 10-fold, the researchers found.

The team detected a CHEK2 mutation in 18 blood samples obtained from 1,620 healthy men and women in Europe and North America. This incidence of 1 in 90 is about nine times as high as that of BRCA1 mutations. Easton and his colleagues report their findings in an upcoming Nature Genetics.

The frequency of the CHEK2 mutation is too low to justify screening in the general population, Easton says. However, for people with other breast cancer risk factors–such as a close relative with the disease–genetic screening and counseling “might be of value,” he says.