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

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Abstract

Objective

The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non–small-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 32.14 months for carriers of XPD 312 Asp/Asp and 12.04 months for those with the variant Asn allele (P = .05). In addition, event-free survival was longer for patients with the XPD 312 Asp/Asp genotype compared with patients with Asp/Asn or Asn/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 (P = .03).

Conclusion

The XPD 312 single nucleotide polymorphism is 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.

Micro-Abstract

The presence of single nucleotide polymorphisms (SNPs) in DNA repair genes, such as xeroderma pigmentosum group D (XPD), can impair DNA repair capacity, thereby affecting chemotherapy efficacy and clinical outcome of patients. Assessment of XPD polymorphisms can permit better stratification of patients into more refined risk categories and optimize decision-making for multidisciplinary treatment in locally advanced non-small cell lung cancer (NSCLC).

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