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EDRI Federal Project Inventory:
05804-01 Studies of Persons at High Risk of Cancer–Pharmacogenetic Studies
- Sponsor Organization: NIH/CP
- Project Title: 05804-01 STUDIES OF PERSONS AT HIGH RISK OF CANCER--PHARMACOGENETIC
STUDIES
- Project Focus: HUMAN HEALTH EFFECTS
- Description: Pharmacogenetics involves the study of host susceptibility and
environmental exposure in cancer development. Theunique contribution
of this discipline is that the genes studied are common, the role of
the environment more explicitbecause the mechanism of the polymorphic
enzymes of interest is know, and the study base is the population
rather thanthe family. A broad range of studies of pharmacogenetic
variability and the relationship to carcinogenesis are underway. We
have developed methodologies to perform phenotyping with various probe
drugs (debrisoquine, caffeine, anddextromethorphan). The relationship
of phenotype to genotype has been explored, with major
contributions inunderstanding how various CYP2D6 mutations impact on
the phenotype, including the discovery of a new mutation. We
recognized and documented ethnic and racial variation in putative
genetic susceptibility factors and we havedescribed its implications.
Cancer associations have been studied: with regard to lung cancer,
heterogeneity wasobserved with regard to CYP2D6, and no association
observed for p53, l-myc, CYP1A1, and CYP2E1 polymorphisms. We have
reported one of the first examples of exposure-susceptibility gene
effects relevant to cancer with descriptions ofthe relationship of the
acetylation phenotype to 4-aminobiphenyl hemoglobin (ABP) adducts and
tobacco type andquantity. Studies of important exposures such as
dioxin and nicotine that may exhibit harmacogenetic variation havebeen
initiated. New pharmacogenetic hypotheses have been generated for
other cancers: nasopharyngeal carcinoma,colon, breast, prostate, and
head and neck. Case case studies of lung and bladder cancer have been
initiated or plannedto better understand the role of cofactors in
there association.
- References:
- Category: MODELS
- Subcategory: BASIC RESEARCH
- Keywords for Experimental System/Species: HUMAN, LABORATORY STUDY
- Keywords for Experimental Endpoints: CARCINOGENESIS, EXPOSURE MONITORING, CYTOCHROME P450
- Chemical Agents: DIOXIN
- Performing Institution: NCI INTRAMURAL PROGRAM
- Contact: CONTACT PERSON: ELAINE C. LEE; BUILDING 31; 11A21, NATIONAL CANCER
INSTITUTE, NIH,BETHESDA, MD 20892-2590; 301- 496-5515;
LEEE@OD.NCI.NIH.GOV
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