Pharmacogenetic and ethnicity influence on oxaliplatin therapy for colorectal cancer: a meta-analysis

Author:

Shahnam Adel1,Ridha Zainab1,Wiese Michael D2,Kichenadasse Ganessan3,Sorich Michael J4

Affiliation:

1. Medical School, The Australian National University, Building 4, The Canberra Hospital Road, Garran, Canberra, Australia 2605

2. School of Pharmacy & Medical Sciences, University of South Australia, Adelaide, Australia

3. Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, Australia

4. Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, Australia

Abstract

Aims: Oxaliplatin-based chemotherapy for colorectal cancer demonstrates interindividual variability in response, and polymorphisms of ERCC1, ERCC2, XRCC1, GSTP1 and GSTM1 genes may be contributing factors. Additionally, the effect of these genotypes may differ between ethnic groups. Material & Methods: A meta-analysis of the association between these genotypes and response, progression-free survival and overall survival (OS) for patients with colorectal cancer treated with oxaliplatin-based therapy is reported. Results: ERCC1 C118T (TT vs CC OS [hazard ratio (HR): 2.59; p = 0.001]), ERCC2 A2251C (CC or AC vs AA OS [HR: 1.53; p = 0.04]) and GSTP1 A313G (GG vs AA OS, [HR: 0.47; p < 0.001]) polymorphisms were associated with survival. The effect size may be larger for ERCC1 C118T and XRCC1 G1196A in Asian compared with Caucasian populations. No association was apparent for the GSTM1 genotype. Conclusion: ERCC1 C118T, ERCC2 A2251C and GSTP1 A313G polymorphisms were associated with clinical outcomes

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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