A meta-analytic review of ERCC1/MDR1 polymorphism and chemosensitivity to platinum in patients with advanced non-small cell lung cancer

Background Platinum-based regimens are used as standard first-line chemotherapy in non-small cell lung cancer （NSCLC） patients.To study if pharmacogenetic approach may allow a tailored selection of platinum chemotherapy for advanced NSCLC,we performed a meta-analysis to compare chemosensitivity to platinum with different ERCC1 C118T7 MDR1 C3435T single-nucleotide polymorphism（SNP）. Methods Relevant studies were identified by searching the PubMed,Embase,Cochrane,OVID,Springer,EBSCO and CNKI databases.Inclusion criteria were patients with advanced NSCLC who received platinum-based chemotherapy,an evaluated polymorphism of ERCC/MDR1 and overall response rate.We excluded duplicate publications,letters and review articles.The RevMan 4.2 and STATA 11 package were used to do comprehensive quantitative assessment. Results A total of 11 studies were included in this meta-analysis.For studies evaluating ERCC1 C118T,test for heterogeneity was done（χ;=13.41,P=0.1）,and the odds ratio（OR） for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 1.50（95%CI 1.09-2.06,P=0.01）.In four studies evaluating MDR1 polymorphism,test for heterogeneity was also done（χ;=3.22,P=0.36）,and the OR for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 2.30（95%CI 1.44-3.68,P=0.0005）. Conclusions The results indicated that platinum-based chemotherapy sensitivity was significantly associated with polymorphism of ERCC1 C118T and MDR1 C3435T SNP.In further perspective studies,the ERCC1/MDR1 SNPs might serve as simple and less invasive biomarkers for personalized chemotherapy with platinum-based anticancer drugs.