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Background: Oral cancer is the third most common cancer in India. It is a multifactorial disease. Cells with defective mismatch repair (MMR) mechanisms cannot correct genetic errors that occur during cellular replication, resulting in a reduction in the fidelity of DNA repair. The objective of this study is to investigate the role of polymorphic variants in MMR gene human MutS homolog-2 (hMSH2) in oral squamous cell carcinoma (OSCC) and associated clinicopathological features in Malayalam speaking population from Kerala. Materials and Methods: Patients diagnosed with OSCC, without superimposed premalignant and other malignant conditions were selected for polymorphism screening of hMSH2 gene. Two single nucleotide polymorphisms (SNPs), rs2303428 (hMSH2-6C/T) located at −6 of the 3′ splice acceptor site of exon 13 and rs61756463 (hMSH2 471C/A) located in exon 3 of hMSH2 were selected based on their functional relevance. Results: Polymorphism screening of hMSH2 gene suggests that rs2303428 was associated with both allelic and genotypic combinations with OSCC. In allelic level, the T allele was associated (P = 0.009) with OR of 2.86, whereas in genotypic level the TT genotype was found to be significantly associated (P = 0.012). In silico prediction of functional implication of this SNP indicated altered transcriptional regulation with functional significance score of 0.176. Although assessing the intergroup comparison within OSCC patients for age (≤50 and >50), gender and histo-differentiation grading, we could not find any association with any of these variables. Conclusion: Certain polymorphic variants in the MMR gene hMSH2 can result in OSCC in Malayalam speaking south Indian population and could indicate defective repair mechanism or Microsatellite instability. Distribution of rs2303428 allele had clear ethnic distribution across world population.
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