Hereditary nonpolyposis colorectal cancer

Abstract

Hereditary nonpolyposis colorectal cancer(HNPCC) is one of the most common cancer predisposition syndromes. Mismatch repair genes, such as hMSH2 and hMLH1, have been identified as causative genes for most HNPCC cases. When we examined the hMLH1 and hMSH2 genes on PCR-SSCP, 9 of the 15(60%) cases satisfying the Amsterdam criteria and 3 of the 22(13.6%) cases with the Japanese clinical criteria showed germline mutations, indicating a significant difference of the detection rate. Interestingly, the mutation frequency of hMSH2(11/12) is much higher than that of hMLH1(1/12). Alterations of TGF-beta RII(A)10 were found in 8(57%) adenomas and 11(85%) cancers, and they were seen at an earlier stage of adenomas, suggesting a strong association of TGF-beta RII alterations with adenoma formation in HNPCC.