XPD, APE1, and MUTYH polymorphisms increase head and neck cancer risk: effect of gene-gene and gene-environment interactions.

In the present study, we investigated the effect of the DNA repair gene polymorphisms XPD Asp312Asn (G>A), APE1 Asp148Glu (T>G), and MUTYH Tyr165Cys (G>A) on the risk for head and neck cancer (HNC) in association with tobacco use in a population of Northeast India. The study subjects comprised of 80 HNC patients and 92 healthy controls. Genotyping was performed using amplification refractory mutation system-PCR (ARMS-PCR) for XPD Asp312Asn (G>A) and PCR using confronting two-pair primers (PCR-CTPP) for APE1 Asp148Glu (T>G) and MUTYH Tyr165Cys (G>A). The XPD Asp/Asn genotype increased the risk for HNC by 2-fold (odds ratio, OR = 2.072; 95 % CI, 1.025-4.190; p < 0.05). Interaction between APE1 Asp/Asp and XPD Asp/Asn as well as MUTYH Tyr/Tyr and XPD Asp/Asn genotypes further increased the risk by 2.9 (OR = 2.97; 95 % CI, 1.16-7.61; p < 0.05) and 2.3 (OR = 2.37; 95 % CI, 1.11-5.10; p < 0.05) folds, respectively. The risk was further increased in heavy smokers with the XPD Asp/Asn genotype and heavy tobacco chewers with XPD Asn/Asn genotype by 7.7-fold (OR = 7.749; 95 % CI, 2.53-23.70; p < 0.05) and 10-fold (OR = 10; 95 % CI, 1.26-79.13; p < 0.05), respectively. We thus conclude that the XPD Asp312Asn and APE1 Asp148Glu polymorphisms increase the risk for HNC in association with smoking and/or tobacco chewing in the population under study.