Abstract
Polymorphisms in the MDM2 309 (T>G) and TP53 72 (G>C) genes are reported to increase the susceptibility to head and neck cancer (HNC) in various populations. The risk for HNC is also strongly associated with etiologic habits such as smoking, alcohol consumption and/or chewing of betel quid (BQ). In a case-control study, we investigated the significance of the above polymorphisms alone, and upon interaction with one another as well as with various etiologic habits in determining HNC risk in a Northeast Indian population. Genotyping at 309 MDM2 and 72 TP53 in 122 HNC patients and 86 cancer free healthy controls was performed by PCR using allele specific primers, and the results were confirmed by DNA sequencing. Individuals with the GG mutant allele of MDM2 showed a higher risk for HNC in comparison to those with the TT wild type allele (OR=1.9, 95%CI: 1.1-3.3) (p=0.022). The risk was further increased in females by ~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 dose- dependent increase in HNC risk, irrespective of the MDM2 genotype. MDM2 genotype could serve as an important predictive biomarker for HNC risk in the population of Northeast India.
Highlights
Head and neck cancers (HNC) constitute the sixth most common cancer world-wide (Macha et al, 2014) and occur widely in developing countries like India (Dikshit et al, 2012; Joshi et al, 2014)
Odds ratio adjusted with age, gender, smoking, betel quid chewing and alcohol consumption were considered in the subsequent unconditional logistic regression analyses to evaluate associations between genetic polymorphisms and head and neck cancer (HNC) risk in the case-control analysis (Table 1)
In our study it was clearly visible that HNC risk associated with murine double minute 2 (MDM2) 309 GG polymorphism was 1.91 fold which indicates that 309MDM2 could be used as a predictive biomarker for the Northeast Indian population (Table 1)
Summary
Head and neck cancers (HNC) constitute the sixth most common cancer world-wide (Macha et al, 2014) and occur widely in developing countries like India (Dikshit et al, 2012; Joshi et al, 2014). The most-well documented among these are genetic factors and exposure to various etiologic agents (Yu et al, 2011) These agents include smoking and alcohol consumption in Western countries and use of smokeless tobacco, areca nut and/or betel quid (BQ) in Southeast Asia. Polymorphisms in the MDM2 309 (T>G) and TP53 72 (G>C) genes are reported to increase the susceptibility to head and neck cancer (HNC) in various populations. In a case-control study, we investigated the significance of the above polymorphisms alone, and upon interaction with one another as well as with various etiologic habits in determining HNC risk in a Northeast Indian population. BQ- chewers and alcohol consumers showed statistically significant and dosedependent increase in HNC risk, irrespective of the MDM2 genotype. Conclusions: MDM2 genotype could serve as an important predictive biomarker for HNC risk in the population of Northeast India
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