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Meta-Analysis
. 2015 Nov 20:5:16482.
doi: 10.1038/srep16482.

Predictive assessment in pharmacogenetics of XRCC1 gene on clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy

Zhengrong Yuan  1   2 , Jiao Li  3 , Ruiqi Hu  1 , Yang Jiao  1 , Yingying Han  1 , Qiang Weng  1
Affiliations
Meta-Analysis

Predictive assessment in pharmacogenetics of XRCC1 gene on clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy

Zhengrong Yuan et al. Sci Rep. .

Abstract

Published data have shown inconsistent results about the pharmacogenetics of XRCC1 gene on clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy. This meta-analysis aimed to summarize published findings and provide more reliable association. A total of 53 eligible studies including 7433 patients were included. Patients bearing the favorable TrpTrp and TrpArg genotypes of Arg194Trp were more likely to better response rates to platinum-based chemotherapy compared to those with the unfavorable ArgArg genotype (TrpTrp+TrpArg vs. ArgArg: odds ratio (OR) = 2.02, 95% CI, 1.66-2.45). The GlnGln and GlnArg genotypes of Arg399Gln were significantly associated with the poorer response rates compared to those with the ArgArg genotype (GlnGln +GlnArg vs. ArgArg: OR = 0.68, 95% CI, 0.54-0.86). The GlnGln genotype might be more closely associated with shorter survival time and higher risks of death for patients (GlnGln vs. ArgArg: hazard ratio (HR) = 1.14, 95% CI, 0.75-1.75). Our cumulative meta-analyses indicated a distinct apparent trend toward a better response rate for Arg194Trp, but a poorer response rate in Arg399Gln. These findings indicate a predictive role of XRCC1 polymorphisms in clinical outcomes. The use of XRCC1 polymorphisms as predictive factor of clinical outcomes in personalized chemotherapy treatment requires further verification from large well-designed pharmacogenetics studies.

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Figures

Figure 1
Figure 1. The flow chart of literatures search and selection of included studies.
Figure 2
Figure 2. Forest plots of clinical outcomes in advanced lung cancer patients treated with platinum-based chemotherapy by the XRCC1 Arg194Trp polymorphism.
(A) Odds ratios (ORs) (and its 95% confidence interval (CI)) of objective response rate (ORR) stratified by study quality levels for TrpTrp+TrpArg vs. ArgArg. (B). Hazard ratios (HRs) (and its 95% CI) of overall survival (OS) for TrpTrp vs. ArgArg. (C). HRs (and its 95% CI) of median progression-free survival (PFS) for TrpTrp vs. ArgArg.
Figure 3
Figure 3. Forest plots of clinical outcomes in advanced lung cancer patients treated with platinum-based chemotherapy by the XRCC1 Arg399Gln polymorphism.
(A) Odds ratios (ORs) (and its 95% confidence interval (CI)) of objective response rate (ORR) stratified by ethnicity for GlnGln+GlnArg vs. ArgArg. (B) Hazard ratios (HRs) (and its 95% CI) of overall survival (OS) stratified by ethnicity for GlnGln vs. ArgArg. (C) HRs (and its 95% CI) of median progression-free survival (PFS) stratified by ethnicity for GlnGln vs. ArgArg.
Figure 4
Figure 4. Forest plot of cumulative meta-analysis to sort out the time-tendency of clinical outcomes in advanced lung cancer patients treated with platinum-based chemotherapy by the XRCC1 Arg194Trp genetic polymorphism (Odds ratios (ORs) and its 95% confidence interval (CI) of objective response rate (ORR) for TrpTrp+TrpArg vs. ArgArg).
Figure 5
Figure 5. Forest plot of cumulative meta-analysis to sort out the time-tendency of clinical outcomes in advanced lung cancer patients treated with platinum-based chemotherapy by the XRCC1 Arg399Gln genetic polymorphism (Odds ratios (ORs) and its 95% confidence interval (CI) of objective response rate (ORR) stratified by ethnicity for GlnGln+GlnArg vs. ArgArg).
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