Genetic susceptibility testing for breast and ovarian cancer: a progress report

The recent identification of genes that predispose their carriers to breast and ovarian cancer promises to shed light on the biology of cancer susceptibility. Individuals with mutations in the BRCA1 gene on chromosome 17 and the BRCA2 gene on chromosome 13 have four to eight times the risk of developing breast cancer as women in the general population. The many mutations that have been identified in both genes are predicted to produce a truncated, presumably nonfunctional, protein. Individuals of Ashkenazi Jewish decent have been found to carry specific BRCA1 and BRCA2 mutations. The sequences of BRCA1 and BRCA2 are not similar to any other previously cloned genes. Investigations are underway to elucidate the biological function of these genes. In the meantime, these genes offer the opportunity for members of high incidence cancer families to decide whether to undergo predisposition testing. There is a paucity of data to guide physicians in making follow-up recommendations to those who are found to be carrying a mutation. Thus, decisions about testing are personal and demand pretest education and counseling about the risks, benefits, and limitations. Further research into testing decisions and their outcome is greatly needed.