Trial Information

Pharmacogenetic Determinants Of Treatment Response In Children

Pharmacogenetics is that discipline devoted to elucidating the genetic determinants of drug
response. Particularly in the area of drug metabolism, many genes exhibit genetic
polymorphism; that is, a stable percentage of the population (which generally differs by
ethnic group) is deficient in the functional expression of the enzyme involved, and the
deficiency is typically inherited as an autosomal recessive trait. With currently known
polymorphisms in drug metabolism, the percentage of homozygous deficient individuals ranges
from 0.3% to as many as 90% of the population, depending on the enzyme and the ethnic group.

Our prior studies have revealed multigenic pharmacogenetic models that are significantly
predictive of various drug response phenotypes (e.g., drug resistance, drug clearance, drug
toxicity, disease response) in children with ALL. The large number of candidate loci and the
relatively small number of patients illustrate the fact that larger sample sizes are
required to definitively establish these polygenic models. The fact that there were
significant race/genotype interactions, such that predictions differed in whites vs blacks,
highlights the need for adequate numbers of patients within racial and ethnic groups to
allow differential analysis of genotypic predictors after adjusting for confounding
demographic factors in pharmacogenetic studies via stratified design and analyses.