CHROMOSOME 2P LINKAGE ANALYSIS IN HEREDITARY NONPOLYPOSIS COLON-CANCER

Hereditary non-polyposis colon cancer (HNPCC) comprises 2-6% of the to tal colorectal cancer burden. Two families are described that show lin kage between the HNPCC susceptibility gene and the markers D2S123 and D2S119 on chromosome 2p, producing multipoint lod scores of 3.62 and 3 .83, respectively, in the largest pedigree. In our third family the mu ltipoint lod scores for D2S123 and D2S119, -2.97 and -3.12, excluded l ocalization of a susceptibility gene in this region indicating that th ere is at least one more gene that causes predisposition to HNPCC. The exclusion was based on at least one genotype for an individual who ha d multiple primary colon and extracolonic tumours and could not be con sidered to have had common forms of cancer. Our results therefore enco urage further gene mapping to pursue the localization of additional HN PCC genes. These findings confirm the presence of the susceptibility g ene for HNPCC, COCAl, on chromosome 2p. They allow the immediate ident ification of a subset of HNPCC families, and provide the means for pre symptomatic testing of family members if sufficient number of members are available for study.