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

ABSTRACT

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 C118T/ 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(2) = 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(2) = 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.