Clinical impact of molecular genetic diagnosis, genetic counseling, and management of hereditary cancer - Part II: Hereditary nonpolyposis colorectalcarcinoma as a model

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common her editary form of colorectal carcinoma (CRC) and may account for 5-10% of the total CRC burden. The discovery of DNA mismatch repair (MMR) genes, inclus ive of hMSH2, hMLH1, hPMS2, and hMSH6, has enabled the identification of wh o has and who does not have inordinately increased susceptibility to CRC as well as a litany of extracolonic cancers. Mutation testing has focused on hMSH2 and hMLH1, the most common mutations in HNPCC. The protocol for DNA t esting and DNA-based genetic counseling is described in Part I of this stud y. One hundred ninety-nine bloodline relatives were tested and counseled fr om five hMLH1 and two hMSH2 families. Their major reason for seeking geneti c counseling and DNA testing was to inform their children and other loved o nes of their mutation status. Those who sought counseling overestimated the ir risk for inheriting the mutation and showed a high rate of interest in p rophylactic surgery, and many were greatly concerned about insurance discri mination. Knowledge about HNPCC, its molecular genetic diagnosis, surveilla nce and management opportunities, and genetic counseling implications are s till emerging, all in the face of a greater need for physician education re garding all facets of hereditary cancer. (C) 1999 American Cancer Society.