CYTOKINE GENE POLYMORPHISMS AND THEIR ASSOCIATION WITH ORAL SQUAMOUS CELL CARCINOMA (OSCC): A NORTH INDIAN STUDY

Maneesh Kumar Gupta, Nibha Sagar, Rajeev Pant and Monisha Banerjee*

ABSTRACT

Oral Squamous Cell Carcinoma (OSCC), the eighth most common cancer worldwide has several risk factors such as alcohol, tobacco and smoking. Oral cancer involves production of cytokines, growth factors and adhesion molecules which promote optimal growth conditions for cancerous cells. The present study was undertaken to evaluate association of cytokine gene polymorphisms with oral cancer. Genotyping of SNPs viz. IL-6-597G/A (rs1800797), TNF-α-308G/A (rs1800629), IL-1β-511C/T (rs16944) and IL-1RN Variable Number of Tandem Repeats (VNTR) in intron 2 was carried out in 140 healthy age/sex matched control subjects and 130 oral cancer patients by PCR-RFLP. Genotype and allele frequencies were calculated and statistically analyzed by chi-square (χ2) using SPSS (ver.21.0). Gene-gene interaction, pairwise linkage disequilibrium (LD) based on ‘D’ statistics and correlation coefficients (r2) of frequencies were analyzed using SHEsis (ver. Online). Genotypic frequencies of IL-6, IL-1β and IL-1RN and allelic frequency of IL-6 showed significant association with oral cancer in north Indian population (p<0.001). Therefore, genetic polymorphisms in associated genes can be used as markers to predict oral cancer susceptibility. Gene-gene interaction analysis showed that individuals with SNP combinations T G G I* and T G G II* of IL-1β-511 C/T, IL-6-597A/G, TNF-α-308G/A and IL-1RN polymorphisms increase the risk of OSCC upto 18.7 and 7.3 folds respectively in the study population. This is probably the first report from India showing the combinatorial effect of these gene polymorphisms and OSCC susceptibility. The study will help to predict individuals at risk of developing OSCC and will provide leads for other cancers as well.

Keywords: Oral Squamous Cell Carcinoma; OSCC; IL-6; TNF-?; IL-1?; IL-1RN; North Indian population.