Correlation of DNA Repair Gene Polymorphisms With Clinical Outcome in Patients With Locally Advanced Non–Small-Cell Lung Cancer Receiving Induction Chemotherapy Followed by Surgery

Objective: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunitM1(RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-Bnonesmall-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. Materials and Methods: A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival. Results: The median survival was 32.14months for carriers of XPD 312 Asp/ Asp and 12.04months for those with the variant Asn allele (P =.05). In addition, event-free survival was longer for patients with the XPD31 2Asp/Asp genotype compared with patients with Asp/Asn orAsn/Asn (P=.03).A similar but nonsignificant trend was observed for the XPD 751 genotype. In a multivariate analysis, complete resection and age emerged as prognostic factors for overall survival; in patients with incomplete resection or exploratory thoracotomy, XPD 312 was the most significant prognostic factor (P¼.03). Conclusion: The XPD 312 single nucleotide polymorphismis a prognostic factor for survival in patients with locally advanced NSCLC receiving induction chemotherapy followed by surgery. The Asn allele is associated with unfavorable outcome and could be used for better stratification of patients.