Colon cancer is a well-known feature of familial polyposis coli. Cancer of the colon occurred in 7 members of 4 successive generations of the family reported by Kluge (1964), leading him to suggest a simple genetic basis for colonic cancer independent of polyposis. The combination of colonic and endometrial cancer has been observed in many families.
A number sign (#) is used with this entry because mutations in several different genes have been identified in colorectal cancer. Mutations in a single gene result in a marked predisposition to colorectal cancer in 2 distinct syndromes: familial adenomatous polyposis (FAP; 175100) and hereditary nonpolyposis colorectal cancer (HNPCC; see 120435). FAP is caused by mutations in the APC gene (611731), whereas HNPCC is caused by mutations in several genes, including MSH2 (609309), MLH1 (120436), PMS1 (600258), PMS2 (600259), MSH6 (600678), TFGBR2 (190182), and MLH3 (604395). Epigenetic silencing of MSH2 results in a form of HNPCC (see HNPCC8, 613244). Other colorectal cancer syndromes include autosomal recessive adenomatous polyposis (608456), which is caused by mutations in the MUTYH gene (604933), and oligodontia-colorectal cancer syndrome (608615), which is caused by mutations in the AXIN2 gene (604025). The CHEK2 gene (604373) has been implicated in susceptibility to colorectal cancer in Finnish patients. A germline mutation in the PLA2G2A gene (172411) was identified in a patient with colorectal cancer. In addition, somatic mutations in many different genes, including KRAS (190070), PIK3CA (171834), BRAF (164757), CTNNB1 (116806), AXIN2 (604025), AKT1 (164730), MCC (159350), MYH11 (160745), and PARK2 (602544) have been identified in colorectal cancer.
Genomewide association studies have shown that common alleles of SMAD7 (602932) influence colorectal cancer risk; see CRCS3, 612229. Additionally, susceptibility loci for colorectal cancer have been mapped to chromosomes 9q22.2-q31.2 (CRCS1; 608812), 8q24 (CRCS2; 611469), 15q13.3 (CRCS4; 601228), 10p14 (CRCS5; 612230), 8q23.3 (CRCS6; 612231), 11q23 (CRCS7; 612232), 14q22 (CRCS8; 612589), 16q22 (CRCS9; 612590), 19q13 (CRCS10; 612591), and 20p12 (CRCS11; 612592).