Role of ERCC5 promoter polymorphisms in response to platinum-based chemotherapy in patients with advanced non-small-cell lung cancer.

The ERCC5 gene plays an important role in the nucleotide excision repair pathway that recognizes and removes platinum-DNA adducts. We aimed to examine whether ERCC5 promoter polymorphisms contribute toward intervariations in the platinum treatment response in patients with advanced non-small-cell lung cancer (NSCLC). We evaluated the association between three tag-single nucleotide polymorphisms in the ERCC5 promoter region (rs2094258, rs751402, and rs2296147, respectively) and the efficacy of chemotherapy in 228 advanced NSCLC patients. We found that the rs751402 AA genotype was associated with a better treatment response [AA vs. AG+GG: odds ratio (OR)=2.74, 95% confidence interval (CI) 1.04-7.26, P=0.036) in all NSCLC patients, which was more evident in the subgroup of patients with squamous cell carcinoma (AA vs. GG: OR=6.40, 95% CI 1.15-35.50, P=0.043; AA vs. AG+GG: OR=6.12, 95% CI 1.15-32.52, P=0.019). No statistically significant association was found between rs2094258 and rs2296147 polymorphisms and treatment response. Our results suggested that the ERCC5 rs751402 AA genotype increased the chemotherapy response in advanced NSCLC, especially in patients with squamous cell carcinoma. Further and larger scale studies are still required to provide more comprehensive information on ERCC5 promoter variations in the clinical outcome of NSCLC patients treated with platinum regimens.