Polymorphism in the hMSH2 gene (gISV12-6T > C) is a prognostic factor in non-small cell lung cancer

Abstract

Genetic polymorphisms at the genes involved in mismatch repair may determine individual's susceptibility to cancer initiation and progression. However, the prognostic significance of hMSH2 gIVS12-6T>C polymorphism (T-C substitution at the -6 intronic splice acceptor site of exon 13) in non-small cell lung cancer (NSCLC) remains unclear. Therefore, we investigated the frequency of hMSH2 gIVS12-6T>C polymorphism in 156 NSCLC patients and 235 cancer-free individuals matched for age, gender and smoking habit. The correlations between hMSH2 genotypes and protein expression and survival of the patients were also analyzed. The frequencies of hMSH2 genotypes T/T, T/C, and C/C were 37.4%, 43.0%, and 19.6%, respectively, and the variant (C) allele was represented at a significantly higher frequency in the general Taiwanese population than in non-Asian populations (P<0.0001, chi(2) test). No significant difference in hMSH2 genotype distribution was found between NSCLC patients and cancer-free controls (P=0.255, multivariate logistic regression). However, the homozygous wild-type T/T genotype was significantly associated with a poor prognosis (P=0.007, log-rank test). Our study showed that the frequency of the variant C allele was significantly higher in the general Taiwanese population than in non-Asian populations and the T/T genotype of hMSH2 gIVS12-6T>C polymorphism was a poor prognostic factor in NSCLC patients.