MDM2 and TP53 Polymorphisms as Predictive Markers for Head and Neck Cancer in Northeast Indian Population: Effect of Gene-Gene and Gene-Environment Interactions

Background: Polymorphisms in the MDM2 309 (T>G) and TP53 72 (G>C) genes are reported to increasethe susceptibility to head and neck cancer (HNC) in various populations. The risk for HNC is also stronglyassociated with etiologic habits such as smoking, alcohol consumption and/or chewing of betel quid (BQ). In acase-control study, we investigated the significance of the above polymorphisms alone, and upon interaction withone another as well as with various etiologic habits in determining HNC risk in a Northeast Indian population.Materials and
Methods: Genotyping at 309 MDM2 and 72 TP53 in 122 HNC patients and 86 cancer free healthycontrols was performed by PCR using allele specific primers, and the results were confirmed by DNA sequencing.
Results: Individuals with the GG mutant allele of MDM2 showed a higher risk for HNC in comparison to thosewith the TT wild type allele (OR=1.9, 95%CI: 1.1-3.3) (p=0.022). The risk was further increased in femalesby ~4-fold (OR=4.6, 95% CI: 1.1-19.4) (P=0.04). TP53 polymorphism did not contribute to HNC risk alone;however, interaction between the TP53 GC and MDM2 GG genotypes resulted in significant risk (OR=4.9, 95%CI: 0.2-105.1) (p=0.04). Smokers, BQ- chewers and alcohol consumers showed statistically significant and dosedependentincrease in HNC risk, irrespective of the MDM2 genotype.
Conclusions: MDM2 genotype could serveas an important predictive biomarker for HNC risk in the population of Northeast India.