Pharmacogenetics in colorectal cancer: a systematic review

Abstract

Pharmacological treatment of colorectal cancer has improved survival rates in recent years. Individual genetic variation in genes associated with metabolism and targets of commonly used drugs can be responsible for variability in treatment outcome and toxicity. Diverse study designs have been used and heterogeneous end points evaluated by studies assessing the association of genetic markers with treatment outcome. We conducted this systematic review, including 51 studies, to present a comprehensive overview and draw further conclusions. To facilitate comparison of reported study results, risk estimates for observed genetic variants in 33 key genes are presented using defined reference categories and recalculated risk estimates based on data provided in original publications, where necessary. Overall, evidence indicates associations of the UGT1A1* 28 variant genotype with toxicity after irinotecan treatment, mutations in GSTP1-105 with improved treatment outcome and the XPD-751 variant genotype with poor treatment outcome after oxaliplatin treatment, and amplification of the EGFR gene with improved treatment outcome after therapy with monoclonal antibodies. Adequately powered prospective investigations designed specifically for pharmacogenetics are needed.