Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 5, pp 1287–1295

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

  • Wan Zhao
  • Lingmin Hu
  • Jiali Xu
  • Hongbing Shen
  • Zhibin Hu
  • Hongxia Ma
  • Yongqian Shu
  • Yongfeng Shao
  • Yongmei Yin
Original Article

DOI: 10.1007/s00280-013-2127-8

Cite this article as:
Zhao, W., Hu, L., Xu, J. et al. Cancer Chemother Pharmacol (2013) 71: 1287. doi:10.1007/s00280-013-2127-8

Abstract

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.

Keywords

Polymorphism Base excision repair Non-small cell lung cancer Chemotherapy Prognosis 

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Wan Zhao
    • 1
  • Lingmin Hu
    • 2
  • Jiali Xu
    • 3
  • Hongbing Shen
    • 2
  • Zhibin Hu
    • 2
  • Hongxia Ma
    • 2
  • Yongqian Shu
    • 3
  • Yongfeng Shao
    • 4
  • Yongmei Yin
    • 3
  1. 1.Department of OncologyBenQ Medical Center, Nanjing Medical UniversitySuzhouChina
  2. 2.Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public HealthNanjing Medical UniversityNanjingChina
  3. 3.Department of OncologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  4. 4.Department of Thoracic and Cardiac SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina