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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.    Methods  A 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.    Results  Twenty-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.

plos one

Polymorphisms in XPD Gene Could Predict Clinical Outcome of Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer Patients: A Meta-Analysis of 24 Studies