Polymorphisms in the base excision repair pathway modulate prognosis of platinum-based chemotherapy in advanced non-small cell lung cancer

• Published in: Cancer chemotherapy and pharmacology Vol. 71; no. 5; pp. 1287 - 1295
• Main Authors: Zhao, Wan, Hu, Lingmin, Xu, Jiali, Shen, Hongbing, Hu, Zhibin, Ma, Hongxia, Shu, Yongqian, Shao, Yongfeng, Yin, Yongmei
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.05.2013; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Biological and medical sciences; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Disease-Free Survival; DNA Repair - genetics; DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics; DNA-Binding Proteins - genetics; Female; Genotype; Humans; Logistic Models; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Oncology; Original Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Platinum Compounds - administration & dosage; Pneumology; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - genetics; Polymorphism, Single Nucleotide; Prognosis; Proportional Hazards Models; Survival Rate; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum; X-ray Repair Cross Complementing Protein 1; Chemotherapy; Prognosis; Base excision repair; Non-small cell lung cancer; Polymorphism; Lung disease; Genetic variability; Respiratory disease; Lung cancer; Genotype; Nucleotide excision repair; Malignant tumor; non-small cell lung carcinoma; Treatment; Platinum; Bronchus disease; Advanced stage; Cancer
• ISSN: 0344-5704; 1432-0843; 1432-0843
• DOI: 10.1007/s00280-013-2127-8

Purpose Platinum-based chemotherapy is the most common treatment for patients with advanced non-small cell lung cancer (NSCLC). Genetic polymorphisms in the base excision repair (BER) pathway are suspected to influence the response of patients to this type of therapy. In this study, we investigated whether nonsynonymous single nucleotide polymorphisms (SNPs) in the BER pathway were associated with the response, progression-free survival (PFS) and overall survival (OS) of NSCLC patients following platinum-based chemotherapy. Methods We used TaqMan to genotype four SNPs ( APE1 Asp148Glu, PARP1 Va1762Ala, XRCC1 Arg194Trp and XRCC1 Arg399Gln) in 147 patients with advanced NSCLC who had undergone routine platinum-based chemotherapy. Results Logistic regression analysis showed that subjects with the XRCC1 -399 A allele had a significantly better response to platinum-based chemotherapy than those with the XRCC1 -399 GG genotype (AA/AG vs. GG: adjusted OR = 2.35, 95 % CI = 1.11–5.00). Furthermore, multivariate Cox proportional hazard regression analysis showed that the PARP1 -762 CC genotype was a significantly unfavorable prognostic factor for PFS (CC vs. CT/TT: adjusted HR = 1.90, 95 % CI = 1.02–3.52). In contrast, the APE1 -148 GG genotype was a significantly protective prognostic factor for OS (GG vs. TT: adjusted HR = 0.33, 95 % CI = 0.12–0.92). Conclusions We found that XRCC1 Arg399Gln, PARP1 Va1762Ala and APE1 Asp148Glu SNPs in the BER pathway may influence the prognosis of advanced NSCLC patients following platinum-based chemotherapy.