Polymorphisms of XRCC1 and XRCC2 DNA Repair Genes and Interaction with Environmental Factors Influence the Risk of Nasopharyngeal Carcinoma in Northeast India

Abstract

Multiple genetic and environmental factors have been reported to play key role in the development of nasopharyngeal carcinoma (NPC). Here, we investigated interactions of <em>XRCC1 </em>Arg399Gln and <em>XRCC2 </em>Arg188His polymorphisms and environmental factors in modulating susceptibility to NPC in Northeast India. One-hundred NPC patients, 90 first-degree relatives of patients and 120 controls were enrolled in the study. <em>XRCC1 </em>Arg399Gln and <em>XRCC2 </em>Arg188His polymorphisms were determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. The <em>XRCC1 </em>Gln/Gln genotype showed increased risk (OR=2.76; P<0.024) of NPC. However, individuals with both <em>XRCC1 </em>and <em>XRCC2 </em>polymorphic variants had 3.2 fold elevated risk (P<0.041). An enhanced risk of NPC was also observed in smoked meat (OR=4.07; P=0.004) and fermented fish consumers (OR=4.34, P=0.001), and tobacco-betel quid chewers (OR=7.00; P=0.0001) carrying <em>XRCC1 </em>polymorphic variants. However, smokers carrying defective <em>XRCC1 </em>gene showed the highest risk (OR = 7.47; P<0.0001). On MDR analysis, the best model for NPC risk was the five-factor model combination of <em>XRCC1 </em>variant genotype, fermented fish, smoked meat, smoking and chewing (CVC=10/10; TBA=0.636; P<0.0001); whereas in interaction entropy graphs, smoked meat and tobacco chewing showed synergistic interactions with <em>XRCC1</em>. These findings suggest that interaction of genetic and environmental factors might increase susceptibility to NPC in Northeast Indian populations.