Abstract
Background Platinum-based chemotherapy plays an antitumor role by damaging DNA. X-ray repair crosscomplementing protein 1 (XRCC1) participates in DNA repair and thus affects the sensitivity to platinum drugs. Two polymorphisms of XRCC1, rs25487 (Arg399Gln) and rs1799782 (Arg194Trp), have been widely studied for the association with clinical outcomes of platinum-based chemotherapy in Asian patients with non-small-cell lung cancer (NSCLC), but the results remain inconclusive. Thus, we performed the present meta-analysis. Methods Literature search was performed in PubMed, Web of Science, and EMBASE up to June 2019. Odds ratios (ORs) for objective response ratio (ORR), Cox proportional hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS), and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the association strengths between XRCC1 polymorphisms and clinical outcomes. Comparisons were performed in homozygous, heterozygous, dominant, and recessive models. Results Finally, a total of 23 studies involving 5567 patients were included in the meta-analysis. Compared to ArgArg of rs25487, GlnGln (OR = 1.71, 95% CI: 1.16-2.52, p = .007, I2 = 56.8%) and GlnArg (OR = 1.23, 95% CI: 1.07-1.40, p = .003, I2 = 29.0%) were associated with higher ORR. Meanwhile, GlnGln indicated a favorable OS (HR = 0.60, 95% CI: 0.40-0.88) and PFS (HR = 0.64, 95% CI: 0.46-0.90). We also found positive associations between rs1799782 and ORR in all comparison models with low between-study heterogeneity. The association strength increased with the number of variant alleles (TrpTrp vs. ArgArg: OR = 1.73, 95% CI:1.31-2.27; TrpArg vs. ArgArg: OR = 1.28, 95% CI: 1.06-1.55), suggesting a gene dosage effect. In addition, TrpTrp predicted a longer OS. Conclusion Our results showed that rs25487 and rs1799782 of XRCC1 are potential markers to predict clinical outcomes of platinum-based chemotherapy in Asian patients with NSCLC.
Highlights
Lung cancer is the most prevalence malignant tumor and the leading cause of cancer deaths worldwide
We aim to evaluate the association between these two polymorphisms in X-ray repair crosscomplementing protein 1 (XRCC1) and clinical outcomes of non-small-cell lung cancer (NSCLC) treated with platinumbased chemotherapy in Asian populations
A total of 121 potentially relevant articles were retrieved from literature search, and 23 studies[18,19,20,21,22,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41] comprised of 5567 NSCLC patients were eligible and included in our analysis (Figure 1)
Summary
Lung cancer is the most prevalence malignant tumor and the leading cause of cancer deaths worldwide It accounts for about 13% of newly diagnosed cancers and is responsible for 17.6% of cancer-related deaths each year[1]. Two polymorphisms of XRCC1, rs25487 (Arg399Gln) and rs1799782 (Arg194Trp), have been widely studied for the association with clinical outcomes of platinum-based chemotherapy in Asian patients with non-small-cell lung cancer (NSCLC), but the results remain inconclusive. Odds ratios (ORs) for objective response ratio (ORR), Cox proportional hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS), and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the association strengths between XRCC1 polymorphisms and clinical outcomes. Our results showed that rs25487 and rs1799782 of XRCC1 are potential markers to predict clinical outcomes of platinum-based chemotherapy in Asian patients with NSCLC
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