Hereditary non-polyposis colorectal cancer (HNPCC), an inherited cancer predisposition syndrome, has been associated with germline mutations in DNA mismatch repair (MMR) genes. However, because all mutation carriers of hMLH1/hMSH2 do not account for CRC susceptibility, modifying genes may play a role in the variation of disease expression. In this study, we determined the GSTM1 and GSTT1 genotypes in 104 family members representing 19 Korean HNPCCs carrying hMLH1/hMSH2 mutation, and investigated the influence of GSTM1 and GSTT1 geno-/phenotype status on both age at diagnosis of CRC and cancer occurrence. The overall frequency of the GSTM1 and GSTT1 geno-/phenotype in 55 non-carriers, compared with that in mutation carriers (n=49), was not significantly different, and no significant correlation was found between mean age at diagnosis and the allelomorphs encoding the GSTM1 or GSTT1 enzymes. However, a comparison of the allele frequencies of GSTM1 in affected (n=30) and unaffected (n=19) mutation carriers revealed a significant difference, as the null allele was more prevalent in individuals with cancer (p=0.03; odds ratio, 3.7; 95% confidence interval, 1.1-12.7). Our results suggest that the genotypes of GSTM1 are associated with cancer occurrence in Korean HNPCC family members carrying the hMLH1/hMSH2 mutation. However, a bias due to the small sample size of this study cannot be rule out. Although evidence that GST genotypes are associated with increased cancer risk has often been controversial, the genotyping of GSTM1 could have implications for genetic counseling and the management of MMR gene mutation carriers.

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