title: Inherited factors and environmental exposures in cancer risk.
abstract: Carcinogenesis is a multistage process that results from the interaction of carcinogenic exposures, cellular macromolecules (eg, DNA), and endogenous mutational mechanisms. Involved in these processes are metabolic activation and detoxification of chemical carcinogens, genetic sequences of protooncogenes and tumor suppressor genes, and DNA repair, among others. Each of these vary widely among individuals and can be associated with increased cancer risk. Cytochrome P4501A1, P4502E1 and N-acetyl transferase 2 are examples of enzymes involved in the metabolic activation of potential environmental carcinogens such as polycyclic aromatic hydrocarbons, benzene, and aromatic amines, respectively. Germ-line mutations in these genes are common and associated with abnormal enzymatic function that are mechanistically related to quantitative changes in binding of carcinogens to DNA. Allelic frequencies for these mutations vary among different racial and ethnic populations and may explain, in part, differences in cancer rates. Risk assessments attempt to predict cancer rates in humans using mathematical models that are often based upon limited experimental data. They do not generally incorporate the numerous stages of carcinogenesis or interindividual variation. Thus, sensitive and resistant populations are not sufficiently considered. This limits the accuracy of currently applied risk assessment models.
authors.affiliation: Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892.
authors.forename: P G
authors.initials: PG
authors.lastname: Shields
mesh_terms: D000107:Acetylation; D002274:Carcinogens, Environmental / Q000009:adverse effects; D003043:Cocarcinogenesis; D004781:Environmental Exposure; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics; D011083:Polycyclic Compounds / Q000378:metabolism; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D002274:Carcinogens, Environmental; D011083:Polycyclic Compounds