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

• Published in: Clinical lung cancer Vol. 18; no. 2; pp. 178 - 188.e4
• Main Authors: Santarpia, Mariacarmela, Ramirez, Jose Luis, de Aguirre, Itziar, Garrido, Pilar, Pérez Cano, Maria, Queralt, Cristina, Gonzalez-Larriba, Jose Luis, Insa, Amelia, Provencio, Mariano, Isla, Dolores, Camps, Carlos, Blanco, Remei, Moran, Teresa, Rosell, Rafael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2017
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - genetics; Carcinoma, Large Cell - genetics; Carcinoma, Large Cell - mortality; Carcinoma, Large Cell - pathology; Carcinoma, Large Cell - therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Cisplatin - administration & dosage; Combined Modality Therapy; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Docetaxel; Female; Follow-Up Studies; Genotype; Humans; Immunoenzyme Techniques; Induction Chemotherapy; Locally advanced non-small cell lung cancer (NSCLC); Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Male; Middle Aged; Neoadjuvant chemotherapy; Neoplasm Staging; Polymorphism, Single Nucleotide - genetics; Prognosis; Prospective Studies; Ribonucleotide reductase subunit M1 (RRM1); Single nucleotide polymorphisms (SNPs); Survival Rate; Taxoids - administration & dosage; Tumor Suppressor Proteins - genetics; Xeroderma pigmentosum group D (XPD); Xeroderma Pigmentosum Group D Protein - genetics; Neoadjuvant chemotherapy; Locally advanced non-small cell lung cancer (NSCLC); Ribonucleotide reductase subunit M1 (RRM1); Single nucleotide polymorphisms (SNPs); Xeroderma pigmentosum group D (XPD)
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2016.08.007

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). 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. 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. 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). 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.