XRCC3 Thr241Met is associated with response to platinum-based chemotherapy but not survival in advanced non-small cell lung cancer

PLoS One. 2013 Oct 8;8(10):e77005. doi: 10.1371/journal.pone.0077005. eCollection 2013.

Abstract

Background: A lot of studies have investigated the correlation between x-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical outcomes in non-small cell cancer (NSCLC), while the conclusion is still conflicting.

Materials and methods: We conducted this meta-analysis to evaluate the predictive value of XRCC3 Thr241Met polymorphism on response and overall survival of patients with NSCLC. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were used to estimate the association strength.

Results: A total of 14 eligible studies with 2828 patients were identified according to our inclusion criteria. Meta-analysis results showed that carriers of the variant 241Met allele were significantly associated with good response, compared with those harboring the wild 241Thr allele (Met vs. Thr, OR = 1.453, 95% CI: 1.116-1.892, Pheterogeneity = 0.968 and ThrMet+MetMet vs. ThrThr, OR = 1.476, 95% CI: 1.087-2.004, Pheterogeneity = 0.696). This significant association was observed in Caucasian population but not in Asian population. On the other hand, there was no significant association of XRCC3 Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95% CI: 0.929-1.261, Pheterogeneity = 0.564), and there was no difference between Asian and Caucasian population.

Conclusions: These findings suggest a predictive role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy in patients with advanced NSCLC. Additionally, we first report that the XRCC3 Thr241Met polymorphism is associated with response to platinum-based chemotherapy and highlights the prognostic value of the XRCC3 Thr241Met polymorphism.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Platinum / therapeutic use*
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • X-ray repair cross complementing protein 3
  • Platinum

Grants and funding

This work was supported by the National Natural Science Foundation of China (81201830), Natural Science Key Research Foundation of Jiangsu Province (BK2011036) and Natural Science Foundation of Jiangsu Province (BK2010589, BK2011857), China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.