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

• Published in: Clinical cancer research 2011-03, Vol.17 (6), p.1632-1640
• Main Authors: MING YIN, JINGRONG YAN, QINGYI WEI, MARTINEZ-BALIBREA, Eva, GRAZIANO, Francesco, LENZ, Heinz-Josef, KIM, Hyo-Jin, ROBERT, Jacques, IM, Seock-Ah, WANG, Wei-Shu, ETIENNE-GRIMALDI, Marie-Christine
• Format: Article
• Language: English
• Subjects: Alleles; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Disease-Free Survival; DNA-Binding Proteins - genetics; Endonucleases - genetics; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Medical sciences; Organoplatinum Compounds - pharmacology; Pharmacology. Drug treatments; Polymorphism, Genetic; Prognosis; Proportional Hazards Models; Risk; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Treatment Outcome; Tumors; Xeroderma Pigmentosum Group D Protein - genetics
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-10-2169

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. 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. 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). 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.