Chromosome 2p linkage analysis in hereditary non‐polyposis colon cancer

Hereditary non‐polyposis colon cancer (HNPCC) comprises 2‐6% of the total colorectal cancer burden. Two families are described that show linkage 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 multipoint lod scores for D2S123 and D2S119, ‐2.97 and ‐3.12, excluded localization of a susceptibility gene in this region indicating that there is at least one more gene that causes predisposition to HNPCC. The exclusion was based on at least one genotype for an individual who had multiple primary colon and extracolonic tumours and could not be considered to have had common forms of cancer. Our results therefore encourage further gene mapping to pursue the localization of additional HNPCC genes. These findings confirm the presence of the susceptibility gene for HNPCC, COCAl, on chromosome 2p. They allow the immediate identification of a subset of HNPCC families, and provide the means for presymptomatic testing of family members if sufficient number of members are available for study.