Allelic Expression of Phase II Metabolizing Enzymes and Relationship to Irinotecan Toxicity

Many drugs are associated with variable response rates and, of the 1,200 drugs approved for use in the United States, about 15% are associated with adverse drug responses (Jorde, Carey, & Bamshad, 2010c). Often, variable response and risk for toxicity can be explained because of differences in genes and in the proteins encoded by those genes. Single nucleotide polymorphisms (SNPs) responsible for variable expression can be found in genes encoding for drug targets (receptors) or in genes responsible for drug disposition, including those that encode metabolizing enzymes or transporter molecules (Jorde et al., 2010c; Kuo, Lee, & Ma, 2009; Ma & Lu, 2011). Although pharmacogenetics usually refers to drug interactions based on a relatively small number of genes, pharmacogenomics is the preferred term because it refers to interactions within the entire complement of genes (Krau, 2013; Ma & Lu, 2011). This article discusses how SNPs in phase II metabolizing enzymes can influence irinotecan-induced toxicity.