Pharmacogenetic Determinants Of Treatment Response In Children
Overview
- Phase
- Not Applicable
- Intervention
- All Participants
- Conditions
- All Malignancies
- Sponsor
- St. Jude Children's Research Hospital
- Enrollment
- 8800
- Locations
- 2
- Primary Endpoint
- To investigate whether genetic polymorphisms in genes encoding proteins involved in the metabolism or effects of drugs or environmental agents influence the disposition or effects of these xenobiotic substrates.
- Status
- Recruiting
- Last Updated
- 3 days ago
Overview
Brief Summary
To investigate whether genetic polymorphisms in genes encoding proteins involved in the metabolism or effects of drugs or environmental agents influence the disposition or effects of these xenobiotic substrates. To investigate the nature of heritability and the genetic basis of pharmacogenetic traits by studying family members of individuals with specific genotypes.
Detailed Description
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.
Investigators
Eligibility Criteria
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
- Not provided
Arms & Interventions
All Participants
All participants enrolled on this study will have blood drawn for genetic testing.
Outcomes
Primary Outcomes
To investigate whether genetic polymorphisms in genes encoding proteins involved in the metabolism or effects of drugs or environmental agents influence the disposition or effects of these xenobiotic substrates.
Time Frame: 28 years