Genetic variability in susceptibility and response to toxicants.
Everyone has a unique combination of polymorphic traits that modify susceptibility and response to drugs, chemicals and carcinogenic exposures. The metabolism of exogenous and endogenous chemical toxins may be modified by inherited and induced variation in CYP (P450), acetyltransferase (NAT) and glutathione S-transferase (GST) genes. We observe that specific 'at risk' genotypes for GSTM1 and NAT1/2 increase risk for bladder cancer among smokers. Genotypic and phenotypic variation in DNA repair may affect risk of somatic mutation and cancer. Variants of base excision and nucleotide excision repair genes (XRCC1 and XPD) appear to modify exposure-induced damage from cigarette smoke and radiation. We are currently engaged in discovering genetic variation in environmental response genes and determining if this variation has any effect on gene function or if it is associated with disease risk. These and other results are discussed in the context of evaluating inherited or acquired susceptibility risk factors for environmentally caused disease.
Miller
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National Institute of Environmental Health Sciences, 111 Alexander Drive, Building 101, Room B323, P.O. Box 12233, C3-03, Research Triangle Park, NC 27709, USA.
Mohrenweiser
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Bell
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D000123:Acetyltransferases / Q000235:genetics; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004260:DNA Repair; D004777:Environment; D020022:Genetic Predisposition to Disease; D023281:Genomics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic; D015262:Xenobiotics / Q000378:metabolism / Q000633:toxicity*
D002273:Carcinogens; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D000123:Acetyltransferases; D005982:Glutathione Transferase