Impact of ERCC1 gene polymorphisms for prognosis in gastric cancer

Abstract

Introduction: ERCC1 is a key enzyme of the nucleotide excision and repair (NER) complex to prevent DNA inter-and intrastrand crosslinks. Genetic alterations of ERCC1 gene are involved in the development and progression of gastrointestinal tumors. We analyzed the prognostic impact of ERCC1 gene polymorphisms in gastric cancer. Methods: There were 112 patients (m:71, f:41) with locally advanced gastric cancer; Methods: There were 112 patients (m:71, f:41) with locally advanced gastric cancer; median age was 66 years (min: 31, max: 87). All patients underwent standaredized gastrectomy with D2 lymphadenectomy. R0 resection rate was 92%; the median number of resected Lymph nodes was 36. For analysis of single nucleotide polymorphisms (SNPs) genomic DNA was extracted from paraffin-embedded tissues. Allelic discrimnation was performed by quantitative real-time PCR. Two allele-specific TaqMan probes in competition were used for amplification of ERCC1 (rsl 1615). Allelic genotyping was correlated with survival. Results: ERCC1 gene polymor phisms for all patients showed the following expression pattern: ERCC1 polymorphism (rs11615) CC: n=41 (36.6%), TT: n=23 (20.5%), CT: n=48 (42.9%). There was no correlation of ERCC1 gene polymorphisms with pT-and pN-category. 5-year survival rate (5-YSR) for all patients was 46%. Gender specific analysis of ERCC1 polymorphisms identified CC genotype for male patients as a significant predictor of a worse survival. Whereas patients with CT-and TT-genotype had a 5-YSR of 53% and 64% respectively, male patients with CC genotype had a 5-YSR of 18% (p=0.015). Conclusion: Analysis of ERCC1 gene polymorphisms in gastric cancer reveals for male patients with CC genotype a significant decline of survival. Whereas the 5-YSR of all patients was 46%, male patients with CC genotype had a 5-YSR of 18% only (p=0.015). There was no correlation with pT-and pN-category. Single nucleotide polymorphisms of ERCC1 (rs11615) could be applied to further estimate prognosis in male patients with gastric cancer.