ERCC1 Gen-Polymorphismus zur Responseprädiktion einer neoadjuvanten Radiochemotherapie beim Ösophaguskarzinom

Abstract

Introduction: To improve survival of patients with locally advanced esophageal cancer neoadjuvant treatment strategies have been developed. Since only patients with major histopathological response benefit from this treatment, predictive markers indicating response or non-response are needed. The gene polymorphisms of ERCC1 were analyzed to predict response to neoadjuvant radiochemotherapy (cis-platin,5-FU,36 Gy) of patients with advanced esophageal cancer. Methods: For analysis of single nucleotide polymorphisms (SNPs) of ERCC1 genomic DNA was extracted from paraffin-embedded tissues of 52 patients. Allelic discrimination was performed by quantitative real-time PCR. Two allelespecific TaqMan probes in competition were used for amplification of the ERCC1 gene. Allelic genotyping was correlated with therapy response. Results: ERCC1 SNP A/G (rs11615) was predictive for therapy response (p < 0.003). Within the AA genotype group of 25 patients 20 (80 %) did not respond to chemoradiation, whereas 14 patients (70 %) of 20 patients with the heterogenous A/G genotype were major responders. The GG genotype comprising 7 patients was not of predictive importance. The ERCC1 polymorphism was significantly (p < 0.02) associated with formation of lymph node metastases. Conclusion: Our data strongly support the role of ERCC1 as a predictive marker for therapy response. Single nucleotide polymorphisms of ERCC1 could be applied to further individualize treatment of patients with locally advanced esophageal cancer.