Abstract

quinone oxidoreductase 1 (NQO1) is part of the antioxidant defence system involved in detoxification. This study aimed to analyze the influence of NQO1 (C609T) genetic polymorphism in non small cell lung cancer (NSCLC)as a putative risk factor. Present study included 100 cases of NSCLC (adenocarcinoma) patients and 100 age and sex matched healthy controls. NQO1 (C609T) genotyping was performed by allele specific PCR for assessment of putative associations with clinical outcome and genotypes of. The association of the polymorphism with the survival of NSCLC patients' was analyzed by Kaplan-Meier method. In Indian NSCLC (adenocarcinoma) patients increased risk of developing NSCLC was found to be associated with NQO1 609TT genotype [OR 3.68(0.90-14.98), RR 2.04(0.78-5.31)] for CT [OR 2.91(1.58- 5.34), RR 1.74(1.23-2.44) p= 0.0005 for CT], for CT+TT [ OR 3.26(1.82-5.82), RR 1.87(1.34-2.61) p<0.0001 for CT+TT]. A significant difference (p=0.0009) was observed in genotype distribution among cases and healthy controls. Patients with CT+TT genotype exhibited a significant poor overall survival compared with patients displaying homozygous CC genotype (p=0.03) and when survival independently compared with CC, TT and CT genotype was also found to be significantly associated (p=0.02). Overall median survival times were CT 6.0 months, TT 8.2 months, and CT + TT (6.4 months)]. The present study revealed that NQO1 CT, TT and CT+TT genotypes may be associated with clinical outcome and risk of developing NSCLC in the Indian population.

Highlights

  • NAD (P) H: quinone oxidoreductase 1 (NQO1) is involved in antioxidant defence system by detoxification of mutagenic agents and carcinogenic quinones by two electron reduction to hydroquinones (Chen et al, 1999; Hou et al, 2005)

  • The present study revealed that NAD(P)H:quinone oxidoreductase 1 (NQO1) CT, TT and CT+TT genotypes may be associated with clinical outcome and risk of developing non small cell lung cancer (NSCLC) in the Indian population

  • Our results suggest that homozygous NQO1 609TT genotype as the risk of developing NSCLC with approximately more than 3.6fold increase while heterozygous NQO1 609CT genotype showed approximately more than 2.9-fold increase than homozygous NQO1 609CC genotype, and were an independent prognostic marker of unfavourable clinical outcome of NSCLC patients

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Summary

Introduction

NAD (P) H: quinone oxidoreductase 1 (NQO1) is involved in antioxidant defence system by detoxification of mutagenic agents and carcinogenic quinones by two electron reduction to hydroquinones (Chen et al, 1999; Hou et al, 2005). C to T Polymorphism at position 609 of exon 6 of the NQO1 that encodes for a proline to serine substitution at position 187 in the amino acid sequence of the protein. The CC genotype of the NQO1 C609T polymorphism is associated with the risk. This study aimed to analyze the influence of NQO1 (C609T) genetic polymorphism in non small cell lung cancer (NSCLC)as a putative risk factor. Results: In Indian NSCLC (adenocarcinoma) patients increased risk of developing NSCLC was found to be associated with NQO1 609TT genotype [OR 3.68(0.90-14.98), RR 2.04(0.78-5.31)] for CT [OR 2.91(1.585.34), RR 1.74(1.23-2.44) p= 0.0005 for CT], for CT+TT [ OR 3.26(1.82-5.82), RR 1.87(1.34-2.61) p

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