[Mutation of human mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) families].

OBJECTIVE

To investigate germline mutations of mismatch repair genes hMLH1 and hMSH2 in 29 HNPCC families.

METHODS

Mutations were detected by PCR-SSCP analysis, and confirmed by DNA sequencing.

RESULTS

(1) In 29 families, the overall mutation rate of these two genes was 31.0% (9/29). Mutation detected in all of the 9 families was located in the hMLH1 gene, indicating that the hMLH1 gene was the main responsible gene in these families. An obvious difference was observed when compared to the mutation rate in the control group (P < 0.01); (2) All of the 10 family members who developed colorectal cancer (CRC) harbored the same mutation as detected in their proband, indicating a strong association between gene mutation and development of CRC. In 29 healthy family members, 5 asymptomatic carriers of mutation were found who were considered as the high-risk populations of CRC.

CONCLUSION

A certain number of HNPCC families can be benefited from the genetic screening for mutation of the mismatch repair genes.