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.

Inclusion Criteria:

- Any patients under evaluation/treatment at St. Jude Children's Research Hospital
(SJCRH)

- Parents or family members of St. Jude patients

- Non patient volunteers

- All study subjects must provide informed consent for participation

- Assent/Consent of the patient (parent) must be provided prior to attempts made by
investigators to enroll a family member of a SJCRH patient

Exclusion Criteria: