A variant of a gene called BARD1 may have a role in triggering breast cancer in some women. A team of researchers in Iceland studied 1,090 Icelandic women who had had breast cancer and compared them with 703 unaffected women to see whether the Cys557Ser variant of BARD1 was associated with an increased risk for breast cancer. They then used a computerized genealogy of the Icelandic population to study the relationships between the Cys557Ser variant and familial clustering of breast cancer.

The protein encoded by BARD1 interacts with the protein encoded by BRCA1; defects in BRCA1 are known to increase the risk of breast cancer, and hence the researchers believed that defects in an interacting protein might have a similar effect. The researchers found that the Cys557Ser allele was nearly twice as common in women with breast cancer as in control women, although the absolute frequency remains small -1.6% in controls versus 2.8% in women with cancer. It was also more common in women who had a family history of breast cancer or who had developed breast cancer more than once.

The most striking result was that carrying the Cys557Ser allele seemed to increase the already high risk of breast cancer in women who had a BRCA2 variant (known as BRCA2 999del5) that accounts for 40% of inherited breast cancer risk in Iceland.

These results, published in the online journal Public Library of Science (PLoS) Medicine, suggest that inheriting the BARD1 Cys557Ser allele increases a woman's breast cancer risk, but for most women the risk is only slight. However, the increase in risk for women who also carry the BRCA2 999del5 mutation is dramatic, and in that context it may be worthwhile developing a clinical test for the BARD1 Cys557Ser allele. The authors caution that these findings need to be confirmed in other groups of patients before anyone is routinely tested for the BARD1 variant.

SOURCE:
PLoS Medicine 3(7): e217, 2006 (www.plosmedicine.org)