CYP2E1, GSTO1 and TP53 polymorphisms, response to chemotherapy and survival in advanced non-small cell lung cancer patients

Abstract

Several gene polymorphisms of xenobiotic/drug metabolizing enzymes and TP53 have been studied for the possible association with response to chemotherapy and survival rates of patients with non-small cell lung cancer (NSCLC). However, the studies in this regard are limited and the results are contradictory. In this study, CYP2E1*5B, CYP2E1*6 and CYP2E1*7B, GST01 (A140D) and TP53 (Arg72Pro) polymorphisms and response to platinum based chemotherapy and survival in 137 (125 men and 12 women) advanced stage NSCLC patients have been investigated. Although no significant associations were noted between the gene polymorphisms alone and response to chemotherapy, patients with combined variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP2E1*6 (*1A/*6) responded significantly better than those carrying wild type genotypes to platinum based chemotherapy, p = 0.40. However, we observed that only the patients who had both variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP2E1*6 (*1A/*6) had shorter survival (median, 17.9 months) compared to wild type genotypes (median, 28.1 months) with marginal significance (p = 0.086). Multivariate analysis also revealed that adjusted hazard ratio of death (HR) of only the combined variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP2E1*6 (*1A/*6) increased 51-fold, although not significant, as compared to wild type genotypes (HR, 50.61; 95% CI, 0.44-5789.77, p = 0.105).