The dose-response relationship between cigarette consumption, biochemical markers and risk of lung cancer

The relationship between the number of cigarettes smoked per day and the incidence of lung cancer is linear but, from the multistage model of carcinogenesis, it should be quadratic (upwards curving). We investigated this anomaly in a study of 11,403 male never smokers and current smokers in whom carboxyhaemoglobin (COHb) was measured in all and serum cotinine in 1175. The relationship between the biochemical markers and the reported number of cigarettes per day was approximately linear up to 20 cigarettes per day as expected. But above 20 cigarettes per day the marker levels increased less steeply and were 35% lower than expected in men who smoked more than 40 cigarettes per day. Less smoke is inhaled from each cigarette by men with high daily cigarette consumption than by men with lower consumption. Allowance for this transforms the observed linear dose-response relationship into one consistent with the expected quadratic relationship. The anomaly is explained by the observation that heavier smokers inhale less smoke from each cigarette.