Genetic testing and counseling for hereditary forms of colorectal cancer

The discovery of genes responsible for inherited farms 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(11307K) is associated with s ome familial colorectal cancer in Ashkenazic Jews. For persons at risk for hereditary forms of colorectal cancer, testing algorithms and gene test int erpretations depend on identification of the pedigree germline gene mutatio n. Careful evaluation of the kindred for characteristic aggregation of tumo r types among affected individuals and the availability of affected persons for testing are important issues in implementing genetic testing and follo w-up management. Case reports illustrate the importance of genetic counseli ng as a component of cancer genetic risk assessment. The genetic counseling process includes exploration of patient risk perception, sources of anxiet y related to cancer risk, patient education (specific cancer-related issues , prevention/intervention options), discussion of possible gene test option s, test limitations, and consequences of various gene test outcomes. Cancer 1999;86:2540-50. (C) 1999 American Cancer Society.