ABCB1 genetic polymorphism and risk of upper aerodigestive tract cancers among smokers, tobacco chewers and alcoholics in an Indian population

Abstract

Upper aerodigestive tract (UADT) cancers are associated with the tobacco use and alcohol consumption. Certain toxins and carcinogens causing UADT cancers are found to be substrates of polymorphic ABCB1 gene encoded P-glycoprotein efflux pump. This study investigates the association between ABCB1 gene polymorphism at exon 26 (3435C>T) and risk to UADT cancers in Tamilians, a population of south India. The study included 219 unrelated histopathologically confirmed cases and 210 population-based controls. Genomic DNA was extracted from peripheral leukocytes and genotyped for ABCB1 3435C>T polymorphism by PCR-restriction fragment length polymorphism method. The multivariate logistic regression analyses demonstrated that the homozygous ABCB1 TT genotype was significantly associated with an overall increased risk for developing UADT cancers [odds ratio (OR): 2.53; 95% confidence interval (CI): 1.28-5.02]. Further, the determination of gene-environment interaction by stratified analyses have revealed a significant interaction between the smoking and homozygous TT genotype [(OR: 7.52; CI: 1.50-37.70) and (OR: 16.89; CI: 3.87-73.79) for 11-20 and >20 pack-years, respectively]. The strongest interaction was observed among the regular tobacco chewers (OR: 45.29; CI: 8.94-130.56) homozygous for TT genotype. No suggestion, however, of an interaction between the genotypes and the alcohol consumption on the multiplicative scale was made. The ABCB1 gene polymorphism at exon 26 (3435C>T) may be one of the risk factors for susceptibility to UADT cancers. Furthermore, the significant interaction among habitual smokers and tobacco chewers, homozygous for TT genotype modulates the risk to UADT cancers in the Tamilian population of south India.