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Pharmacogenetic Association between XRCC1 Polymorphisms and Response to Platinum-Based Chemotherapy in Asian Patients with NSCLC: A Meta-Analysis

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机构: [1]Department of Oncology, Peace Hospital of Changzhi Medical College, Changzhi, Shanxi 046000, China [2]Department of Intervention, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510005, China
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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. Copyright © 2020 Ningning Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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出版当年[2019]版:
大类 | 3 区 生物
小类 | 3 区 生物工程与应用微生物 4 区 医学:研究与实验
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 生物工程与应用微生物 4 区 医学:研究与实验
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出版当年[2018]版:
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
最新[2023]版:
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q3 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者机构: [1]Department of Oncology, Peace Hospital of Changzhi Medical College, Changzhi, Shanxi 046000, China
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