Common Variations of DNA Repair Genes are Associated with Response to Platinum-based Chemotherapy in NSCLCs

Xian-Dong Li,Yi-Jie Zhang,Xue-Yan Wu,Hong-Bing Li,Ji-Chang Han

doi:10.7314/apjcp.2013.14.1.145

Abstract

Individual differences in chemosensitivity and clinical outcome of non-small-cell lung cancer (NSCLC) patients may be induced by host inherited factors. We investigated the impact of XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp and XPD Lys751Gln gene polymorphisms on the efficacy of platinum-based chemotherapy in NSCLC patients. A total of 496 were consecutively selected from the Affiliated Hospital of Nantong University between Jan. 2003 and Nov. 2006, and all patients were followed-up until Nov. 2011. The genotyping of XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp and XPD Lys751Gln was conducted by duplex polymerase-chain-reaction with the confronting-two-pair primer methods. Individuals with XPD 312 C/T+T/T and XPD 711 C/T+T/T exhibited poor responses to chemotherapy when compared with the wild- type genotype, with adjusted ORs(95% CI) of 0.67(0.38-0.97) and 0.54(0.35-0.96), respectively. Cox regression showed the median PFS and OS of patients of XPD 312 C/T+T/T genotype and XPD 711 C/T+T/T genotype to be significantly lower than those with wild-type homozygous genotype. We found polymorphisms in XPD to be associated with response to platinum-based chemotherapy in NSCLC, and our findings provide information for therapeutic decisions for individualized therapy.

Highlights

Lung cancer is one of the most common cancers worldwide and the leading cause of cancer death in China and many other countries of the world, which is classified as small-cell lung cancer and non-small-cell lung cancer (NSCLC), with the latter accounting for 80% of primary lung cancers (IARC, 2008)
We evaluated whether common a higher apoptotic response to UV compared with those
Several studies of advanced NSCLC patients treated with platinum-based suggested that Xeroderma pigmentosum group D (XPD) 751Gln substitutions might produce chemotherapy

Summary

Introduction

Lung cancer is one of the most common cancers worldwide and the leading cause of cancer death in China and many other countries of the world, which is classified as small-cell lung cancer and non-small-cell lung cancer (NSCLC), with the latter accounting for 80% of primary lung cancers (IARC, 2008). Platinum agents are used for chemotherapy cause DNA damage and cell death by activating the cell signaling pathways (Azuma et al, 2007), the host cellular DNA repair capacity may influence the outcome of NSCLC (Gurubhagavatula et al, 2004; Lord et al, 2002). Efficiency of DNA damage repair systems is considered to be one of the most important mechanisms affecting interindividuals differences in response to chemotherapy and clinical outcome of patients. Common variants in the XPD gene are found to be correlated with various cancer risk (Duan et al, 2012; Mi et al, 2012; Zhang et al, 2012), and it is reported that the XPD gene polymorphisms are significantly associated with chemotherapy effect of cancer (Provencio et al, 2012; Zhang et al, 2012). Few studies explored the association of polymorphisms of XPD Arg156Arg and XPD Asp711Asp with the clinical outcomes of NSCLC patients

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