Lack of Influence of MGMT Codon Leu84Phe and Codon Ileu143Val Polymorphisms on Esophageal Cancer Risk in the Kashmir Valley

Abstract

The enzyme encoded by the MGMT gene is involved in the repair of alkylated lesions formed in DNA bycarcinogenic nitrosamines. Since dietary items consumed by the Kashmiri population contain high concentrationsof these agents, it is biologically plausible that MGMT polymorphic variants may be associated with their riskof esophageal cancer. The present study was performed to assess whether non-synonymous SNPS at codonLeu84Phe and codon Ileu143Val of the MGMT gene, close to the active site of the protein, might be linked topredisposition of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain reactionrestrictionfragment length polymorphism on 92 cases and 77 healthy controls. Codon 84 and codon 143 SNPs ofthe MGMT gene were not associated with any increase in risk. While the frequency of the Phe allele at codon 84in cases was (0.16), slightly higher than controls (0.12), the difference was not statistically significant. Similarly,the frequency of Valine allele in cases at codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, nosignificant association of MGMT genotypes with the clinicopatholgic variables of esophageal cancer patients wasobserved. In conclusion, MGMT variants at codon 84 and codon143 may not be involved in the susceptibility ofthe Kashmiri population to esophageal cancer.