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Purpose  Xeroderma pigmentosum group D ( XPD ) codes for a DNA helicase involved in nucleotide excision repair that removes platinum-induced DNA damage. Genetic polymorphisms of XPD may affect DNA repair capacity and lead to individual differences in the outcome of patients after chemotherapy. This study aims to identify whether  XPD  polymorphisms affect clinical efficacy among advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.    Experimental Design  353 stage III-IV NSCLC patients receiving platinum-based chemotherapy as the first-line treatment were enrolled in this study. Four potentially functional  XPD  polymorphisms ( Arg 156 Arg ,  Asp 312 Asn ,  Asp 711 Asp  and  Lys 751 Gln ) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or PCR-based sequencing.    Results  Variant genotypes of  XPD Asp 312 Asn, Asp 711 Asp  and  Lys 751 Gln  were significantly associated with poorer NSCLC survival ( P  = 0.006, 0.006, 0.014, respectively, by log-rank test). The most common haplotype GCA (in order of  Asp 312 Asn, Asp 711 Asp  and  Lys 751 Gln ) also exhibited significant risk effect on NSCLC survival (log-rank  P  = 0.001). This effect was more predominant for patients with stage IIIB disease ( P  = 2.21×10 −4 , log-rank test). Increased risks for variant haplotypes of  XPD  were also observed among patients with performance status of 0–1 and patients with adenocarcinoma. However, no significant associations were found between these polymorphisms, chemotherapy response and PFS.    Conclusions  Our study provides evidence for the predictive role of  XPD Asp 312 Asn, Asp 711 Asp  and  Lys 751 Gln  polymorphisms/haplotype on NSCLC prognosis in inoperable advanced NSCLC patients treated with platinum-based chemotherapy.

Effect of Polymorphisms in XPD on Clinical Outcomes of Platinum-Based Chemotherapy for Chinese Non-Small Cell Lung Cancer Patients