Genome-wide disease association study in chewing tobacco associated oral cancers.

With a view to identify genomic risk variants in chewing-tobacco associated oral cancer patients, a genome-wide association study was conducted in patients of Indian ethnicity with long term tobacco chewing habit. We analyzed 55 oral cancer patients and 92 healthy controls for single nucleotide polymorphisms, using high throughput microarray Illumina Infinium II Assay platform and Human CNV370k-bead chip containing 370,000 single nucleotide polymorphisms. The PLINK software platform defined 298 SNPs with minor allele frequency of several genes significantly increased in oral cancer patients as compared to the controls (p<0.001). Illumina Genome Viewer Software Version 3.2.9, further delineated 93 SNPs with p-values ranging from 9.3×10(-4) to 1.38×10(-5) and Odd's ratio of 2.18-8.48, associated with 70 genes. Analysis using Kyoto Encyclopedia of Genes and Genome Pathway database, indicated SNP association with several genes including GRIK2, RASGRP3, CAMK4, SYK, RAPTOR, FHIT, DCC, active in signal transduction; MMP2, CNTNAP2, PTPRJ associated with tumor cell migration; and apoptotic gene IRAK3. The data indicates an inherent role for the genetic constitution of individuals in oral carcinogenesis, with the genomic variants contributing to increased risk or susceptibility to oral cancer.