Metabolic polymorphisms and carcinogen-DNA adduct formation in human populations

Metabolic polymorphisms have long been recognized as important determinants of carcinogen susceptibility and recent efforts have shown that interindividual differences in specific cytochromes P450, acetyltransferases, sulfotransferases and glutathione S-transferases are often disproportionately represented in epidemiological studies between cancer cases and controls. Concomitantly, biomonitoring of carcinogen-DNA adducts in human tissues using immunochemical, 32P-postlabelling, fluorescence, and mass spectrometric methods have recently provided direct evidence of human exposure to genotoxic aromatic and heterocyclic amines, polycyclic hydrocarbons, alkylating agents, and endogenous products. However, a combined approach is now needed in order to assess the relevance of these findings to cancer etiology, to identify high-risk individuals, and to provide better health monitoring, earlier diagnosis, and cancer prevention. Using this paradigm, results are presented that implicate specific aromatic amines, heterocyclic amines, and polycyclic aromatic hydrocarbons in the etiology of human urinary bladder, colon, and laryngeal cancers.