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

<div><h3>Purpose</h3><p>Xeroderma pigmentosum group D (<em>XPD</em>) 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 <em>XPD</em> polymorphisms affect clinical efficacy among advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.</p> <h3>Experimental Design</h3><p>353 stage III-IV NSCLC patients receiving platinum-based chemotherapy as the first-line treatment were enrolled in this study. Four potentially functional <em>XPD</em> polymorphisms (<em>Arg¹⁵⁶Arg</em>, <em>Asp³¹²Asn</em>, <em>Asp⁷¹¹Asp</em> and <em>Lys⁷⁵¹Gln</em>) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or PCR-based sequencing.</p> <h3>Results</h3><p>Variant genotypes of <em>XPD Asp³¹²Asn, Asp⁷¹¹Asp</em> and <em>Lys⁷⁵¹Gln</em> were significantly associated with poorer NSCLC survival (<em>P</em> = 0.006, 0.006, 0.014, respectively, by log-rank test). The most common haplotype GCA (in order of <em>Asp³¹²Asn, Asp⁷¹¹Asp</em> and <em>Lys⁷⁵¹Gln</em>) also exhibited significant risk effect on NSCLC survival (log-rank <em>P</em> = 0.001). This effect was more predominant for patients with stage IIIB disease (<em>P</em> = 2.21×10⁻⁴, log-rank test). Increased risks for variant haplotypes of <em>XPD</em> 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.</p> <h3>Conclusions</h3><p>Our study provides evidence for the predictive role of <em>XPD Asp³¹²Asn, Asp⁷¹¹Asp</em> and <em>Lys⁷⁵¹Gln</em> polymorphisms/haplotype on NSCLC prognosis in inoperable advanced NSCLC patients treated with platinum-based chemotherapy.</p>