Metabolic Phase I (CYPs) and Phase II (GSTs) Gene Polymorphisms and Their Interaction with Environmental Factors in Nasopharyngeal Cancer from the Ethnic Population of Northeast India.

Abstract

Multiple genetic and environmental factors and their interaction are believed to contribute in the pathogenesis of Nasopharyngeal Cancer (NPC). We investigate the role of Metabolic Phase I (CYPs) and Phase II (GSTs) gene polymorphisms, gene-gene and gene-environmental interaction in modulating the susceptibility to NPC in Northeast India. To determine the association of metabolic gene polymorphisms and environmental habits, 123 cases and 189 controls blood/swab samples were used for PCR and confirmed by Sanger sequencing. Analysis for GSTM1 and GSTT1 gene polymorphism was done by multiplex PCR. The T3801C in the 3'- flanking region of CYP1A1 gene was detected by PCR-RFLP method. The Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The GSTM1 null genotype alone (OR=2.76) was significantly associated with NPC risk (P<0.0001). The combinations of GSTM1 null and GSTT1 null genotypes also higher, 3.77 fold (P<0.0001), risk of NPC, while GSTM1 null genotype along with CYP1A1 T3801C TC+CC genotype had 3.22 (P=0.001) fold risk. The most remarkable risk was seen among individual carrying GSTM1 null, GSTT1 null genotypes and CYP1A1 T3801C TC+CC genotypes (OR=5.71, P=0.001). Further; analyses demonstrate an enhanced risk of NPC in smoked meat (OR=5.56, P<0.0001) and fermented fish consumers (OR=5.73, P<0.0001) carrying GSTM1 null genotype. An elevated risk of NPC was noted in smokers (OR=12.67, P<0.0001) and chewers (OR=5.68, P<0.0001) with GSTM1 null genotype. However, smokers had the highest risk of NPC among individuals carrying GSTT1 null genotype (OR=4.46, P=0.001) or CYP1A1 T3801C TC+CC genotype (OR=7.13, P<0.0001). The association of null genotypes and mutations of metabolic neutralizing genes along with the environmental habits (tobacco smokers and chewers, smoke meat, fermented fishes) can be used as a possible biomarker for early detection and preventive measure of NPC.