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.
Vineis
P
P
Unit of Cancer Epidemiology, University of Torino, Turin, Italy.
Kogevinas
M
M
Simonato
L
L
Brennan
P
P
Boffetta
P
P
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