In a 20-year prospective study on British doctors, smoking habits were ascertained by questionnaire and lung cancer incidence was monitored. Among cigarette smokers who started smoking at ages 16-25 and who smoked 40 or less per day, the annual lung cancer incidence in the age range 40-79 was:0.273X10(-12). (cigarettes/day+6)2. (age--22.5)4.5. The form of the dependence on dose in this relationship is subject not only to random error but also to serious systematic biases, which are discussed. However, there was certainly some statistically significant (P less than 0.01) upward curvature of the dose-response relationship in the range 0-40 cigarettes/day, which is what might be expected if more that one of the "stages" (in the multistage genesis of bronchial carcinoma) was strongly affected by smoking. If a higher than linear dose-response relationship exists between dose per bronchial cell and age-specific risk per bronchial cell, this may help explain why bronchial carcinomas chiefly arise in the upper bronchi, for dilution effects might then protect the larger areas lower in the bronchial tree.
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