MOLECULAR-BIOLOGY OF SMOKING-ASSOCIATED C ANCER

Adducts, formed by carcinogens of tobacco smoke with DNA, can be detec ted by means of molecular techniques and are used as marker of interna l exposure. Carcinogen-DNA adducts produce specific mutations in tumor -suppressor genes (e.g. p53) and oncogenes (e.g. ras), which can be in volved in tumor initiation or in later stages of tumor progression (e. g. evolution of an invasive phenotype). Benzo(a)pyrene, an important c arcinogen of tobacco smoke, induces GT transversions, as demonstrated in in vitro systems and animal models. Mutations in the p53- or ras-ge ne are more common in human tumors of the lung, head and neck, bladder and pancreas in smokers than in non-smokers. Molecular biology of can cer gains increasing significance in clinical practice since 1.) the p resence of certain mutations confers an unfavorable prognosis to malig nant disease (e.g. ras mutations in lung cancer), 2.) ras and p53 muta tions often occur early during tumor development and can thus facilita te diagnosis of malignant disease, and 3.) minimal residual disease ca n be detected using molecular techniques. After resection of cancer of the head and neck, tumor recurred more frequently in patients with no evidence of residual disease as assessed by pathohistologic criteria than in patients with no evidence of residual disease as evaluated by p53 immunostaining.