Abstract
Data regarding genetic polymorphisms and platinum-based chemotherapy (PBC) treatment outcomes in patients with NSCLC are published at a growing pace, but the results are inconsistent. This meta-analysis integrated eligible candidate genes to better evaluate the pharmacogenetics of PBC in NSCLC patients. Relevant studies were retrieved from PubMed, Chinese National Knowledge Infrastructure and WANFANG databases. A total of 111 articles comprising 18,196 subjects were included for this study. The associations of genetic polymorphisms with treatment outcomes of PBC including overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were determined by analyzing the relative risk (RR), hazard ration (HR), corresponding 95% confidence interval (CI). Eleven polymorphisms in 9 genes, including ERCC1 rs11615 (OS), rs3212986 (ORR), XPA rs1800975 (ORR), XPD rs1052555 (OS, PFS), rs13181 (OS, PFS), XPG rs2296147 (OS), XRCC1 rs1799782 (ORR), XRCC3 rs861539 (ORR), GSTP1 rs1695 (ORR), MTHFR rs1801133 (ORR) and MDR1 rs1045642 (ORR), were found significantly associated with PBC treatment outcomes. These variants were mainly involved in DNA repair (EXCC1, XPA, XPD, XPG, XRCC1 and XRCC3), drug influx and efflux (MDR1), metabolism and detoxification (GSTP1) and DNA synthesis (MTHFR), and might be considered as potential prognostic biomarkers for assessing objective response and progression risk in NSCLC patients receiving platinum-based regimens.
Highlights
With platinum-based chemotherapy (PBC) response and prognosis of patients4–8
We described the meta-analysis findings of associations between genetic polymorphisms and treatment outcomes of NSCLC patients receiving platinum drugs
DNA repair pathways including nucleotide excision repair (NER) and base excision repair (BER) could timely repair the damaged DNA induced by platinum agents and lead to treatment failure122
Summary
With PBC response and prognosis of patients. The accumulation of pharmacogenomics findings calls for a more comprehensive systematic review and meta-analysis to summarize the evidence and to identify the general genetic associations among reported results. A total of 24 single nucleotide polymorphisms (SNPs) of 12 genes (ERCC1, XPA, XPC, XPD, XPG, XRCC1, XRCC3, GSTP1, MTHFR, RRM1, MDR1 and CDA) have been studied in our work. The impacts of these genetic variants on PBC efficacy in NSCLC patients were assessed by evaluating the objective response ratio (ORR), progression-free survival (PFS), and overall survival (OS). We think this comprehensive meta-analysis with robust evidence would fill the gap in the pharmacogenomics of platinum in NSCLC patients
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