Influence of ERCC1 and ERCC4 polymorphisms on response to prognosis in gastric cancer treated with FOLFOX-based chemotherapy.

Abstract

Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1)-excision repair cross-complimentary group 4 (ERCC4) genes have been implicated in the prognosis of various cancers. We conducted a cohort study to investigate the role of ERCC1-ERCC4 gene polymorphisms on the response to chemotherapy and the role of these two gene polymorphisms on the clinical outcomes of gastric cancer. Four hundred forty-seven patients with newly diagnosed and histopathologically confirmed primary gastric cancer were collected in our study and were followed up until March 2012. ERCC1 (rs11615, rs3212986C>A, and rs2298881) and ERCC4 (rs226466C>G, rs2276465, and rs6498486) were selected and genotyped. The overall chemotherapy response rate for treatment was 68 %. Carriers of the rs11615 TT and T allele and ERCC1 rs2298881 CC and C allele had a marginally significantly higher response rate to the chemotherapy. In the Cox proportional hazard model, the hazard ratios (HRs) for overall survival (OS) in patients carrying ERCC1 rs11615 TT genotype and T allele were 0.53 (0.29-0.95) and 0.63 (0.42-0.94), respectively. Similarly, we found a significant decreased risk of death from gastric cancer among patients carrying ERCC1 rs2298881 CC genotype and C allele when compared with CC genotype, and HRs (95% confidence interval (CI)) of OS were 0.50 (0.24-0.98) and 0.62 (0.40-0.96), respectively. Moreover, individuals carrying ERCC1 rs11615 T allele and rs2298881 C allele could decrease a 0.62-fold risk of death from gastric cancer. This study reported a carriage of ERCC1 rs11615, and rs2298881 polymorphism can be used as a predictor of response to folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX)-based chemotherapy in gastric cancer patients.

• Authors: Zheng-mao Lu, Tian-hang Luo, Ming-ming Nie, Guo-en Fang, Li-ye Ma, Xu-chao Xue, Guo Wei, Chong-we Ke, Jian-wei Bi
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 35 Issue 4 Pg. 2941-8 (Apr 2014) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 24318989 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Organoplatinum Compounds
• xeroderma pigmentosum group F protein
• ERCC1 protein, human
• Endonucleases
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• DNA Repair
• DNA-Binding Proteins (genetics)
• Endonucleases (genetics)
• Female
• Fluorouracil (therapeutic use)
• Genotype
• Humans
• Leucovorin (therapeutic use)
• Male
• Middle Aged
• Organoplatinum Compounds (therapeutic use)
• Polymorphism, Single Nucleotide
• Prognosis
• Proportional Hazards Models
• Stomach Neoplasms (drug therapy, genetics, mortality)