Effect of XPC polymorphisms on the response to platinum-based chemotherapy: a meta-analysis

Objective: As an important DNA repair gene, the xeroderma pigmentosum complementation group C (XPC) gene and its functional genetic variants’ relationship with chemotherapy response has been extensively studied. To quantitatively elucidate the genetic impact of the XPC rs2228000 and rs2228001 polymorphisms on the response to platinum-based chemotherapy, the present meta-analysis was conducted. Materials and methods: A systematic literature search was performed in seven cyber databases until February 20, 2019, for all relevant studies that assessed the relationship between XPC polymorphisms and the response to platinum-based chemotherapy. Odds ratios (ORs) with a 95% confidence interval (95% CI) were measured to assess the strength of the association. R programs were developed to perform the statistical analyses, including calculations of pooled estimates, publication bias and sensitivity analyses, and heterogeneity interpretations. Results: A total of 1,615 patients from 10 studies for the rs2228001 polymorphism were winnowed for further statistical analysis. For the rs2228000 polymorphism, 858 samples from six datasets were included. However, this meta-analysis indicated no significant effect of these two XPC polymorphisms on the response to platinum-based chemotherapy. When stratified according to sample size, country or cancer type, no statistical significance for association was identified in all subgroups. Further sensitivity analysis and publication bias assessment ensured the reliability of the meta-analysis. Conclusions: The pooled estimates suggest that neither the rs2228000 polymorphism nor the rs2228001 polymorphism contributes to the genetic predisposition for an altered response to platinum-based chemotherapy. Considering the limitations of our present meta-analysis, more studies with large-scale cohorts and rigorous methods are needed to validate our results.