Molecular polymorphisms in genes associated with cell proliferation and differentiation indicating risk to oral cancer

Abstract

Molecular Polymorphisms in Genes Associated with Cell Proliferation and Differentiation indicating Risk to Oral Cancer newlineOral cancer is the third most common cancer in India, with an annual incidence of 77,003, constituting 53,842 males and 23,161 females; with India contributing 26% of the global oral cancer burden. The risk factors for oral cancer are tobacco, areca nut, alcohol and high risk oncogenic Human Papilloma Viruses 16/18. However, only few individuals with the risk factors develop oral cancer. Hence in addition to lifestyle habits, an inherent role of the genetic constitution with variants predisposes individuals to oral cancer, altering their susceptibility to oral cancer. newlineThe genomic variants are commonly represented as single nucleotide polymorphisms (SNPs), with ten million estimated SNPs in the human genome, and about three million SNPs documented in the SNP database dbSNP. The SNPs are single base changes in the genome, present in gt1-2 % of a given population. We investigated twelve SNPs in genes with biological functions associated with cell proliferation and differentiation. The association of the SNPs to oral cancer was examined in oral cancer patients (n=500) and long term tobacco users as controls (n=500), using allelic discrimination Real-Time PCR and HRM analysis. Increased oral cancer risk was observed for SNPs rs9849237 CC [P = 0.008; OR 1.412 (1.09 1.82)] and rs243865 CT [P = 0.004; OR 1.469 (1.13 1.90)] genotypes; whereas rs9849237 CT [P = 0.034; OR 0.755 (0.58 0.97)], rs243865 CC [P = 0.002; OR 0.669 (0.51-0.86)] and rs10090787 CC [P = 0.049; OR 0.774 (0.60 0.99)] genotypes indicated decreased risk to oral cancer. The other nine SNPs showed equidistribution in both oral cancer and control groups. Our data indicated genotypes and alleles in specific SNPs rs9849237 (CNTN4), rs243865 (MMP2) and rs10090787 (SNTB1) with increased/decreased risk to oral cancer. newline