Translational research on hereditary colon, breast, and ovarian cancers.

Discoveries of inherited cancer susceptibility genes are creating new opportunities for translational cancer control research. Identification of these genes was facilitated by epidemiologic studies of mendelian patterns of cancers in families and advances in laboratory techniques to detect inherited mutations. Tumor suppressor genes were the first cancer-predisposing genes identified, primarily through studies of rare cancers such as hereditary retinoblastoma and Wilms' tumor. Recently, a second class of susceptibility genes, mismatch repair genes such as MSH2 and MLH1, has been shown to be defective in hereditary nonpolyposis colon cancers. Knowledge of these genes and the recently identified BRCA1 gene for hereditary breast/ovarian cancers raises the possibility of cancer-predisposition testing of substantial portions of the general population. Carriers are at high risk of cancer and are candidates for early detection and chemoprevention studies. However, large-scale cancer-predisposition testing poses questions about not only ethical, legal, and social issues, but also technological and logistical challenges. Cancer-predisposition testing is new, and research is needed to maximize benefits while minimizing risks.