Levelling-off of the risk of lung and bladder cancer in heavy smokers: an analysis based on multicentric case-control studies and a metabolic interpretation.
The shape of the dose-response relationship between carcinogenic exposure and cancer risk is a key issue, both from a theoretical (models of carcinogenesis) and practical (risk assessment) point of view. Human populations exposed to Polycyclic Aromatic Hydrocarbons (PAH) via air pollution showed a non-linear relationship between levels of exposure and WBC-DNA adducts. Among highly exposed subjects, the DNA adduct level per unit of exposure was significantly lower than measured at environmental exposures. The same exposure-dose non-linearity was observed in lung DNA from rats exposed to PAH. We have analyzed 11 case-control studies on bladder cancer (4584 incident cases and 9360 hospital controls) and eight case-control studies on lung cancer (5092 incident cases and 6083 population controls), conducted in Europe in recent years. All the studies collected detailed information on smoking histories with a similar methodology. We have estimated the relationship between the number of cigarettes smoked and the risk of cancer, with and without adjustment by duration of smoking. We have observed a levelling-off of the relationship between the number of cigarettes smoked and the relative risks for lung and bladder cancer, both in men and women. The levelling-off occurred at an odds ratio of about 5 for bladder cancer, while it occurs at about 20 for lung cancer (in men). A potential explanation for such levelling-off involves metabolic pathways and individual susceptibility. It has been suggested that some metabolic polymorphisms exert an effect that is more important at low levels of exposure.
Unit of Cancer Epidemiology, University of Torino, Turin, Italy.
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P
Vineis
M
M
Kogevinas
L
L
Simonato
P
P
Brennan
P
P
Boffetta
D000328:Adult; D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D018736:DNA Adducts / Q000378:metabolism; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000378:metabolism
D018736:DNA Adducts