Polymorphisms of ERCC1 C118T/C8092A and MDR1 C3435T predict outcome of platinum-based chemotherapies in advanced non-small cell lung cancer: a meta-analysis.

ABSTRACT

BACKGROUND AND AIMS: With great progress made in individualized chemotherapy, pharmacogenetics is gradually put on the agenda. We performed this meta-analysis to compare outcome to platinum-based chemotherapies in advanced non-small cell lung cancer (NSCLC) with different ERCC1 C118T/C8092A and MDR1 C3435T polymorphisms. METHODS: Relevant studies were identified according to search strategy in this meta-analysis. Inclusion criteria were patients with advanced NSCLC who were receiving platinum-based chemotherapies. We evaluated the relationship between single nucleotide polymorphisms (SNP) and outcome of platinum-based chemotherapies. RevMan and STATA package were used for the comprehensive quantitative analyses. RESULTS: Twenty studies were included in the meta-analysis. There was no significant association between SNPs and objective response or overall survival of platinum-based chemotherapies with CC vs. CT/TT ERCC1 C118T (OR 1.21, 95% CI 0.81-1.82 for objective response; HR 1.09, 95% CI 0.79-1.51 for overall survival); ERCC1 C8092A SNP (OR 0.84, 95% CI 0.59-1.18; HR 1.26, 95% CI 0.68-2.36) and MDR1 C3435T SNP (HR 1.11, 95% CI 0.78-1.56). Ethnic stratification provided the same results. We found a significant difference for MDR1 C3435T (OR 2.22, 95% CI 1.46-3.37; OR 2.63, 95% CI 1.56-4.45 for Asians; OR 1.61, 95% CI 0.79-3.28 for Caucasians). CONCLUSIONS: We found no evidence to support the use of ERCC1 C118T/C8092A polymorphisms as prognostic predictors of platinum-based chemotherapies in NSCLC. For the MDR1 C3435T SNP, a significant association with objective response was detected for CC genotype in overall and Asian populations stratified. Multiple and large-scale studies with ethnic stratification are required for the correlation between biomarkers and tumor prognosis.