The association between the ERCC1/2 polymorphisms and the clinical outcomes of the platinum-based chemotherapy in non-small cell lung cancer (NSCLC): a systematic review and meta-analysis

Abstract

The relationship between the ERCC1/2 single nucleotide polymorphisms (SNPs) and the clinical outcomes of the platinum-based chemotherapy in the non-small cell lung cancer (NSCLC) is still inconsistent and inconclusive despite extensive investigations have been conducted to address this question. In this meta-analysis, we aim to further explore the prognostic value of the ERCC1/2 SNPs in NSCLC by analyzing all currently available evidences. Relevant studies were searched in PubMed, Embase, and China National Knowledge Infrastructure. The inclusion criteria were platinum-based chemotherapy in NSCLC patients and evaluation of clinical outcomes in relation to the ERCC1 C118T, ERCC1 C8092A, ERCC2 Asp312Asn, and ERCC2 Lys751Gln. Clinical outcomes analyzed in this study included the overall response rate, overall survival (OS), and progression-free survival (PFS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard associated with each SNP. A total of 46 studies including 9,407 NSCLC patients were qualified for this meta-analysis. For ERCC1 C118T, the T allele was associated with a poor OS (HR = 1.35, 95% CI = 1.04-1.75); for ERCC2 Asp312Asn, the Asn variant was linked to an unfavorable OS (HR = 2.07, 95% CI = 1.11-3.88); and for ERCC2 Lys751Gln, patients with the Gln variant have a worse OS (HR = 1.22, 95% CI = 1.05-1.41) and PFS (HR = 1.35, 95% CI = 1.07-1.71). In addition, the main findings of the ERCC1/2 SNPs on chemotherapy toxicity were also summarized. This meta-analysis suggested that the ERCC1 C118T, ERCC2 Asp312Asn, and Lys751Gln may be useful biomarkers to predict the clinical outcomes of the platinum-based chemotherapy in NSCLC patients.