Xenobiotic/drug metabolizing enzyme and TP53 polymorphisms and clinical outcome in advanced nonsmall cell lung cancer patients

Authors: VOLKAN KARACAOĞLAN, AHMET OĞUZ ADA, SERDAR BİLGEN, GÜZİDE TUĞBA ÇETİNKAYA, EMRE SOYDAŞ, CELALETTİN SEMİH KUNAK, SİBEL MERYEM ALPAR, MERAL GÜLHAN, MÜMTAZ İŞCAN

Abstract: Background/aim: The association between polymorphisms of xenobiotic/drug metabolizing enzymes and TP53 and response to chemotherapy and survival of patients with nonsmall cell lung cancer (NSCLC) are limited and inconclusive. In this study, CYP2E1*5B, CYP2E1*6, CYP2E1*7B, GSTO1 (A140D), and TP53 (Arg72Pro) polymorphisms and response to platinum-based chemotherapy and survival in 137 advanced stage NSCLC patients were investigated. Materials and methods: Genetic polymorphism analyses were determined by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). Results: The patients with TP53 Pro/Pro variant were more likely to be resistant to chemotherapy than those with Arg/Arg variants with marginal significance (P = 0.066). We also analyzed these gene variants in combination with CYP1A1 (Ile462Val), CYP1B1 (Asn453Ser), GSTM1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) and GSTT1 polymorphic genes that we have previously genotyped in the same patients (Ada et al., Neoplasma, 57, 512-527, 2010). The multivariate analysis revealed that adjusted hazard ratio (HR) of death of the combined variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP1A1 (Ile462Val, Val462Val) increased significantly as compared to wild-type genotypes (HR, 6.03; 95% CI, 1.39-26.04, P = 0.016). Conclusion: These results show that combined variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP1A1 (Ile/Val, Val/Val) are associated with worsening of survival in NSCLC patients.

Keywords: Xenobiotic/drug metabolizing enzymes, TP53, polymorphisms, response to chemotherapy, survival, nonsmall cell lung cancer

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