Cigarette smoking and lung cancer: modeling effect modification of total exposure and intensity

A recent analysis indicates that the excess odds ratio for lung cancer by smoking is described by a function that is linear in pack-years and exponential in the logarithm of smoking intensity and its square (Cancer Epidemiol Biomarkers Prev. 2006;15:517-523). The model suggests that below 15-20 cigarettes per day there is a "direct exposure rate" effect, ie, the excess odds ratio per pack-year for higher intensity (and shorter duration) smokers is greater than for lower-intensity (and longer duration) smokers. Above 20 cigarettes per day, there is an "inverse-exposure-rate" effect, ie, the excess odds ratio per pack-year for higher intensity smokers is smaller than for lower-intensity smokers.

Using pooled data from 2 large case-control studies of lung cancer (the European Smoking and Health Study and the German Radon Study), we evaluated effect modification of the association between smoking and lung cancer.

Interaction effects are very specific. Variations in risk of lung cancer with years since cessation of smoking, age, method of inhalation, and type of cigarette result from interactions with smoking intensity, and not total pack-years. In contrast, risk variations by sex result from the interaction with total pack-years, while intensity effects are homogeneous. Risk variations by age at which smoking started result from interactions with both total pack-years and intensity. All intensity interactions are homogeneous across studies.

The specificity of the interactions may provide clues for the molecular basis of the smoking and lung cancer relationship.