Clinical and genetic features of International Collaborative Group-hereditary nonpolyposis colorectal cancer families and suspected hereditary nonpolyposis colorectal cancer families

Background Hereditary nonpolyposis colorectal cancer (HNPPC) is one of the most common genetic syndrome related with mutation of human mismatch repair genes. This study was to evaluate the clinical significance of suspected hereditary nonpolyposis colorectal cancer (sHNPCC) criteria I and the clinical and genetic features of International Collaborative Group-HNPCC (ICG-HNPCC) and sHNPCC families.Methods Twenty-nine ICG-HNPCC families fulfilling the Amsterdam criteria and 34 sHNPCC families fulfilling the sHNPCC criteria I were collected. PCR-SSCP and DNA sequencing analysis were employed to screen the germline mutations of the hMLH1 and hMSH2 genes in these families.Results The ICG group had more colorectal cancer (CRC) patients per family than did the suspected group (P<0.05). No statistical difference was observed in Lynch classification and familial tumor spectrum. In both groups of families, colorectal cancer was the most frequent malignancy, and carcinomas of the stomach, pancreas and uterus were the three most common extracolonic malignancies. Mutation screening showed that ICG-HNPCC and sHNPCC families had a similar mutation rate (31.0% vs 29.4%, P>0.05), mutation type, and mutation distribution. Comparison of the families with and without mutation showed no significant difference in CRC patients per family, Lynch classification, and tumor spectrum.Conclusions ICG-HNPCC and sHNPCC families that have similar clinical manifestations and genetic basis indicate a similar nature for cancer development. The application of sHNPCC criteria I will facilitate clinical diagnosis and treatment of small families.