The XPD Lys751Gln polymorphism has predictive value in colorectal cancer patients receiving oxaliplatin-based chemotherapy: a systemic review and meta-analysis

Asian Pac J Cancer Prev. 2014;15(22):9699-706. doi: 10.7314/apjcp.2014.15.22.9699.

Abstract

Background: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism regarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performed a meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation and optimize individual chemotherapy.

Materials and methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) were used to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-free survival (PFS) and overall survival (OS).

Results: A total of 17 studies including 2,286 patients met the inclusion criteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response to oxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups. However, poor PFS and OS of CRC patients treated with oxaliplatin-based regimens were significantly related to the XPD 751Gln allele in the dominant model (PFS: HR=2.10, 95%CI: 1.65-2.67; OS: HR=3.18, 95%CI: 1.57-6.47). On stratified analysis by ethnicity, these relationships were more pronounced in Asians (PFS: HR=2.49, 95%CI: 1.79-3.47; OS: HR=5.25, 95%CI: 3.46-7.94) than in Caucasians (PFS: HR=1.73, 95%CI: 1.22-2.46; OS: HR=1.78, 95%CI: 1.06-2.99).

Conclusions: The XPD Lys751Gln polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Humans
  • Organoplatinum Compounds / therapeutic use*
  • Oxaliplatin
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Risk Factors
  • Xeroderma Pigmentosum Group D Protein / genetics*

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human