Objective To estimate the dynamic effect of increasing intensity of smoking and occupational exposure to asbestos on the risk of lung cancer.

Method We used 2026 male cases and 2610 male controls from the ICARE population-based case-control study. Smoking and occupational histories were collected in a detailed face-to-face questionnaire. Occupational exposure to asbestos was assessed using a job exposure matrix. The dynamic effects of the intensity of smoking and asbestos were investigated using a weighted cumulative index of exposure (WCE), which was a weighted sum of the doses of exposure received each year of the exposure history. The dose received each year was the average intensity of exposure (i.e. number of cigarettes smoked per day or asbestos fibre concentration) that year. The time-dependent weight function of each nuisance was estimated using spline functions imposing no prior assumptions on the plausible dynamic effect of the nuisance. The WCE of each nuisance was included in separate logistic regression models adjusted for the other nuisance, age, and department.

Results The estimated weight functions gave for each year of the exposure history, the estimated effect of a one-unit increase in the intensity of exposure on that year, adjusted for the doses received in the other years. Both recent (less than 10 years before diagnosis) and distant (more than 30 years) increases in the asbestos concentration contributed to the risk of lung cancer. Increases that occurred before the age of 30 years had the strongest contribution to the risk. For smoking, recent increases (less than 10 years) in the number of cigarettes smoked per day made an important contribution to the risk of lung cancer, even if distant increases (more than 40 years) also contributed to the risk.

Conclusion Our results give new insights on the dynamic effects of smoking and asbestos on lung cancer.