Genetic testing and counseling for hereditary forms of colorectal cancer

The discovery of genes responsible for inherited forms of colorectal cancer have the potential to improve cancer risk assessment and counseling. Germl ine mutations (nonsense, frameshift) of APC are associated with familial ad enomatous polyposis, an autosomal dominant syndrome, clinically characteriz ed by young onset, hundreds of adenomatous polyps in the colon, and increas ed risk for extracolonic tumors. Mutations in APC are also associated with forms of attenuated familial adenomatous polyposis. Germline mutations in f ive mismatch repair related genes (hMSH2, hMLH1, hMSH6, hPMS1, and hPMS2) c ause hereditary nonpolyposis colorectal cancer and are associated with incr eased risk of somatic genetic alterations and high DNA microsatellite insta bility. Hereditary nonpolyposis colorectal cancer is characterized by young onset colorectal cancer, proximal colon location, and increased risk of ex tracolonic cancers. A missense mutation in APC (I1307K) is associated with some familial colorectal cancer in Ashkenazic Jews. For persons at risk for hereditary forms of colorectal cancer, testing algorithms and gene test in terpretations depend on identification of the pedigree germline gene mutati on. Careful evaluation of the kindred for characteristic aggregation of tum or types among affected individuals and the availability of affected person s for testing are important issues in implementing genetic testing and foll ow-up management. Case reports illustrate the importance of genetic counsel ing as a component of cancer genetic risk assessment. The genetic counselin g process includes exploration of patient risk perception, sources of anxie ty related to cancer risk, patient education (specific cancer-related issue s, prevention/intervention options), discussion of possible gene test optio ns, test limitations, and consequences of various gene rest outcomes. (C) 1 999 American Cancer Society.