Study of New Genetic Mutation

[Mgarr]

Variation to Gene May Triple Breast-Cancer Risk

Published: 07/31/06

MONDAY, July 31 (HealthDay News) -- A mutation of a gene called CHEK2 may triple a woman's risk for developing breast cancer, a new study suggests.

Previous research had found that the CHEK2 mutation -- carried by an estimated 1 percent of white, northern European women -- increased the chances of breast cancer in women at high risk for the disease. However, that risk is still far less than the threat posed by the well-known BRCA1 and BRCA2 mutations.

"They are more important," said Dr. Borge G. Nordestgaard, senior author of the new CHEK2 study and professor of genetic epidemiology at the University of Copenhagen and professor and chief physician of clinical biochemistry at Herlev University Hospital in Denmark. "BRCA1 and 2 are many, many different mutations. This [CHEK2] is just a single mutation," Nordestgaard said.

Still, women who have the CHEK2 mutation may benefit from increased screening for breast cancer, said the study, which was published online July 31 in the Journal of Clinical Oncology. And, women who have the CHEK2 mutation plus the BRCA1 and BRAC2 mutations could have a vastly increased risk and need to be monitored carefully, the researchers said.

One limitation of the new study was that it included only white Danish women, so it's still unclear how prevalent the mutation is among black, Hispanic or other women, or if the risk is the same in these groups.

CHEK2 is a tumor suppressor gene, meaning it repairs damaged DNA and prevents the unregulated division of cells, which can lead to cancer.

Women with breast cancer and a family predisposition to breast cancer are routinely offered screening for mutations to the BRCA1 and 2 genes. Relevant mutations only turn up in less than 25 percent of the women screened.

About 1 percent of American women have a BRCA1 or BRCA2 mutation. According to background information in the new study, these women have up to an 80 percent chance of developing breast cancer during their lifetime and often at a much younger age than women who don't have the mutation. The lifetime risk of developing breast cancer among the general population is about 13 percent.

After BRCA1 and 2, the CHEK2 mutation is the most likely genetic explanation for breast cancer, the researchers said. The mutation has also been associated with prostate and colorectal cancer and is found in 0.5 percent to 1.4 percent of white people in northern Europe.

A 2005 study found that family members of women who carry the CHEK2 mutation and who have had cancer in both breasts have a vastly increased risk of developing breast cancer themselves.

The new study is the first to look at the prevalence of the CHEK2 mutation in the general population and what kind of risk it confers.

The study involved 9,231 Danes who were followed for an average of 34 years as part of the Copenhagen City Heart Study.

In all, 0.5 percent of all participants carried the CHEK2 mutation. Twelve percent of women with the mutation developed breast cancer, compared with 5 percent of non-carriers. After adjusting for other risk factors -- such as age, weight and use of hormone-replacement therapy -- women who carried the mutation were 3.2 times more likely to develop breast cancer than women who had normal CHEK2 genes.

Women who had the mutation and were over 60 years old, overweight and were taking hormone-replacement therapy had a 24 percent chance of developing breast cancer within 10 years.

The study turned up no statistically significant association between the CHEK2 mutation and prostate, colorectal or general cancer risk.

More information

For more on the risks for breast cancer, visit the American Cancer Society.

Last reviewed: 07/31/2006 | Last updated: 07/31/2006