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ERCC1 and ERCC2 Polymorphisms Predict Clinical Outcomes of Oxaliplatin-Based Chemotherapies in Gastric and Colorectal Cancer: A Systemic Review and Meta-analysis

Cited 123 time in Web of Science Cited 140 time in Scopus

Yin, Ming; Yan, Jingrong; Martinez-Balibrea, Eva; Graziano, Francesco; Lenz, Heinz-Josef; Kim, Hyo-Jin; Robert, Jacques; Im, Seock-Ah; Wang, Wei-Shu; Etienne-Grimaldi, Marie-Christine; Wei, Qingyi

Issue Date
American Association for Cancer Research
Clinical Cancer Research, Vol.17 No.6, pp.1632-1640
Purpose: Nucleotide excision repair (NER) modulates platinum-based chemotherapeutic efficacy by removing drug-produced DNA damage. To summarize published data on the association between polymorphisms of NER genes (ERCC1 and ERCC2) and responses to oxaliplatin-based chemotherapies, we carried out a meta-analysis of gastric and colorectal cancer for commonly studied polymorphisms ERCC1 rs11615C>T and ERCC2 rs13181T>G. Patients and Methods: In 17 previously published studies, 1,787 cancer patients were treated with the oxaliplatin-based regimen. Primary outcomes included therapeutic response (TR; i.e., complete response+ partial response vs. stable disease + progressive disease), progression-free survival (PFS), and overall survival (OS). We calculated OR or HR with 95% CIs to estimate the risk or hazard. Results: We found consistent and clinically substantial risk or hazard for TR, PFS, and OS in the oxaliplatin-treated gastric and colorectal cancer patients with an ethnic discrepancy. For ERCC1 rs11615C>T, the T allele was associated with reduced response and poor PFS and OS in Asians (TR: OR = 0.53 and 95% CI = 0.35-0.81; PFS: HR = 1.69 and 95% CI = 1.05-2.70; and OS: HR = 2.03 and 95% CI = 1.60-2.59). For ERCC2 rs13181T>G, the G allele was associated with reduced response and poor PFS and OS in Caucasians (TR: OR = 0.56 and 95% CI = 0.35-0.88; PFS: HR = 1.41 and 95% CI = 1.02-1.95; and OS: HR = 1.42 and 95% CI = 1.11-1.81). Conclusions: NER ERCC1 rs11615C>T and ERCC2 rs13181T>G polymorphisms are useful prognostic factors in oxaliplatin-based treatment of gastric and colorectal cancer. Larger studies and further clinical trials are warranted to confirm these findings. Clin Cancer Res; 17(6); 1632-40. (C) 2011 AACR.
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  • Department of Medicine
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