Abstract
Objective Xeroderma pigmentosum group D (XPD) is an essential gene involved in the nucleotide excision repair (NER) pathway. Two commonly studied single nucleotide polymorphisms (SNPs) of XPD (Lys751Gln, A>C, rs13181; Asp312Asn, G>A, rs1799793) are implicated in the modulation of DNA repair capacity, thus related to the responses to platinum-based chemotherapy. Here we performed a meta-analysis to better evaluate the association between the two XPD SNPs and clinical outcome of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients.MethodsA comprehensive search of PubMed database was conducted to identify relevant articles. Primary outcomes included objective response (i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS) and overall survival (OS). The pooled and 95% confidence intervals (CIs) of ORs (odds ratios) and HRs (hazard ratios) were estimated using the fixed or random effect model.ResultsTwenty-four studies were eligible according to the inclusion criteria. None of the XPD Lys751Gln/Asp312Asn polymorphisms was associated with objective response, PFS or OS in NSCLC patients treated with platinum drugs. However, in stratified analysis by ethnicity, the XPD Lys751Gln (A>C) polymorphism was not significantly associated with increased response in Caucasians (OR = 1.35, 95%CI = 1.0–1.83, P = 0.122 for heterogeneity) but was associated with decreased PFS in Asians (HR = 1.39, 95%CI = 1.07–1.81, P = 0.879 for heterogeneity). Furthermore, a statistically significant difference existed in the estimates of effect between the two ethnicities (P = 0.014 for TR; P<0.001 for PFS).Conclusions XPD Lys751Gln (A>C) may have inverse predictive and prognostic role in platinum-based treatment of NSCLC according to different ethnicities. Further studies are needed to validate our findings.
Highlights
Lung cancer remains the most frequent human malignancy worldwide and represents a leading cause of cancer related death with only 15% of patients surviving five years or more [1]
The detailed eligible criteria were as follows: (1) patients with histologically or pathologically confirmed advanced, recurrent, or metastatic Nonsmall cell lung cancer (NSCLC); (2) the patients were treated with platinum-based chemotherapy; (3) Xeroderma pigmentosum group D (XPD) Lys751Gln or Asp312Asn single nucleotide polymorphism was genotyped; (4) studies provided primary outcomes of interest including objective response, progression-free survival or overall survival
A total of 17 studies including 2,919 patients reported the correlation between XPD polymorphisms and treatment response, 11 studies including 2,001 patients reported XPD polymorphisms and progression-free survival (PFS), and 17 studies including 3,561 patients reported XPD polymorphisms and overall survival (OS)
Summary
Lung cancer remains the most frequent human malignancy worldwide and represents a leading cause of cancer related death with only 15% of patients surviving five years or more [1]. Nonsmall cell lung cancer (NSCLC) accounts for approximately 80% of primary lung cancer and most patients have suffered from advanced disease at the time of diagnosis [2]. The standard chemotherapeutic regimen for the treatment of advanced NSCLC patients is based on the combination of platinum compounds and a third-generation cytotoxic agent [3]. There is considerable heterogeneity in therapeutic efficacy of platinum-based chemotherapy between different patients, and the response rate of platinum doublets is only 25–30% in NSCLC [4]. There is an urgent need to identify genetic markers that could predict the risk of lung cancer and the response of patients to platinum based chemotherapy
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