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 differe4nt ERCC1 Cl18T/ 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/MDIR1 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 Cl18T, test for heterogeneity was done （X2=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 （X2=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 Cl18T 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.