[Individual susceptibility to occupational carcinogens: the evidence from biomonitoring and molecular epidemiology studies].
This paper reviews the literature on the influence of metabolic and DNA repair polymorphisms of biological indicators of genotoxic risk commonly used in biomonitoring occupational exposure to carcinogens. Genetic polymorphisms which influence biomarkers (urinary metabolites, protein and DNA adducts), include P450 cytochromes (CYPs) and glutathione S-transferases (GSTs) in exposure to polycyclic aromatic hydrocarbons (PAHs), and acetyltransferases (NATs) in exposure to aromatic amines (AAs). As regards exposure to benzene, also relevant is the influence of epoxydohydrolase (EPHX) and NAD(P)H quinone oxidoreductase (NQO1) on the urinary excretion of t,t-muconic and phenylmercapturic acids. With respect to occupational exposure to styrene, EPHX significantly influences the levels of Chromosome Aberrations (CAs), strongly predictive genotoxic biomarkers of cancer risk. Some recent studies examine the role of polymorphisms linked to DNA repair genes in the modulation of genotoxic risk associated with PAH exposure, both for life-style (dietary and smoking behaviour) and for occupational reasons. In addition, molecular epidemiology studies (case/control studies) of lung cancer in smokers published since 2000 may also be viewed as representing models of effects due to exposure to carcinogenic mixtures, some of which are present in the working environment (e.g., BaP, benzene, AAs). Almost all studies show the clearcut influence (i.e., increased lung cancer risk with OR > or = 2) of genetic polymorphisms linked to PAH metabolism (in particular, CYPIA1, GSTM1 and P1). Among the risk factors are the different mutagen sensitivity towards, for instance, bleomycin and BaP (tested in vitro), the reduced repair capacity to DNA damage induced by BaP, and increases in some biomarkers of early biological effect (DNA adducts and stable CAs). Other risk factors, such as heredity (siblings of cancer patients have a risk factor > or = 3 with respect to the general population), ethnicity (Chileans > Caucasians; Japanese > Americans) and gender (women > men), have still not been clearly characterized and these are also reported in this paper. It is clear from the above that genetic differences underlie individual susceptibility to lung cancer, whether caused by exposure to tobacco smoke or to occupational carcinogens like PAHs. Some of these indicators of exposure/individual susceptibility can be evaluated in groups at high risk of occupational lung cancer, such as coke-oven and aluminium workers and those exposed to coal tar fumes and soot, etc., with the aim of identifying subjects who are susceptible due to the high concentrations of carcinogens found in their working environment.
Pavanello
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Dipartimento di Medicina Ambientale e Sanità Pubblica, Sezione Medicina del Lavoro, Università degli Studi di Padova.
Clonfero
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D015415:Biomarkers; D002274:Carcinogens, Environmental; D016022:Case-Control Studies; D004249:DNA Damage; D004260:DNA Repair; D004032:Diet; D004198:Disease Susceptibility; D004784:Environmental Monitoring; D062665:Epidemiological Monitoring; D005006:Ethnicity; D005260:Female; D005838:Genotype; D006801:Humans; D008019:Life Style; D008175:Lung Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D008297:Male; D017720:Molecular Epidemiology; D009784:Occupational Diseases / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D016273:Occupational Exposure / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
D015415:Biomarkers; D002274:Carcinogens, Environmental