title: Metabolic phenotypes and colorectal neoplasia.
abstract: It now appears likely that the development of colonic adenomas and carcinomas involves a series of steps in which environmental or endogenous carcinogens induce or promote neoplasia through the accumulation of multiple, specific genetic mutations. Genetic predisposition to this process may take the form of inherited defects in control of cellular proliferation as in familial polyposis coli, or genetically determined polymorphism which affects enzyme activities relevant to the production or detoxication of carcinogens. Genetic effects may also influence levels of hormones and/or their target cell receptors which regulate the metabolic and proliferative activity of colonocytes. This review highlights data suggesting a role for polymorphism associated with xenobiotic acetylation, hydroxylation, and conjugation with glutathione in the metabolism of potential carcinogens, as well as for dehydroepiandrosterone in the metabolic control of cell proliferation. The study of genetically determined polymorphism in colorectal cancer may provide new insights into the epidemiology of cancer and result in new methods for the detection of higher risk groups.
authors.affiliation: Department of Gastroenterology, Queen Elizabeth Hospital, Woodville South, South Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Fettman
authors.forename: R N
authors.initials: RN
authors.lastname: Butler
authors.forename: A J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: I C
authors.initials: IC
authors.lastname: Roberts-Thomson
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics; D011125:Adenomatous Polyposis Coli; D015179:Colorectal Neoplasms / Q000235:genetics*; D003687:Dehydroepiandrosterone / Q000235:genetics; D005979:Glutathione Peroxidase / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D006900:Hydroxylation; D010641:Phenotype; D011110:Polymorphism, Genetic; D012727:Sex Characteristics; D015262:Xenobiotics
chemical_list: D015262:Xenobiotics; D003687:Dehydroepiandrosterone; D005979:Glutathione Peroxidase; D000123:Acetyltransferases; D005982:Glutathione Transferase