Tobacco and cancer: epidemiology and the laboratory.
Tobacco smoke contains many mutagenic and carcinogenic chemicals. Both whole tobacco smoke and extracts induce tumors in experimental animals. Work with carcinogen-macromolecule adducts provided evidence for the action of specific chemicals. Molecular epidemiology studies suggested that point mutations in tumor-suppressor genes (e.g., p53) and oncogenes (e.g., ras) may be specific both for the type of tumor and for the critical environmental exposure. The consistency among investigations on oncogene/tumor-suppressor gene mutations in lung cancer (and other tobacco-related cancers) in smokers is highly suggestive, although we still lack information about the time sequence between exposure, gene mutation, and cancer onset. Current work that deserves emphasis includes investigations revealing that lungs of smokers contain benzo[a]pyrene diol-epoxide-guanine DNA adducts, which are in accordance with the type of mutations found in K-ras or p53 genes (G to T transversions). In addition, DNA in human exfoliated bladder cells showed a derivative of 4-aminobiphenyl as a main adduct; there was also an association between smoking habits (amount and type of tobacco) and the levels of both DNA adducts and hemoglobin adducts formed by aromatic amines. Increasing evidence indicates that genetically based metabolic polymorphisms exert a role in modulating individual susceptibility to the action of tobacco carcinogens. Overall, the weight of evidence strongly supports the causal nature of the association between smoking and cancer and falsifies Fisher's hypothesis that the association was due to confounding by genetic predisposition.
Vineis
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Unit of Cancer Epidemiology, Dipartimento di Scienze Biomediche e Oncologia Umana, Torino, Italy.
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D015986:Confounding Factors, Epidemiologic; D004781:Environmental Exposure; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D017720:Molecular Epidemiology; D017354:Point Mutation; D012907:Smoking / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics