CPD and other self-reported variables reflecting smoking behavior have been used extensively as measures of tobacco exposure in epidemiological studies of lung cancer, including studies on genetic factors. As tobacco smoking is the major risk factor for lung cancer(29), accurate measures of tobacco exposures are essential. However, it is known that assessing smoking exposure using questionnaires will be subject to missclassification(3,30). Studies on the relationship between questionnaire measures of tobacco exposure (e.g. CPD) and biomarkers of tobacco exposure (e.g. cotinine) (4,31-36) have reported a non-linear relationship, particularly among heavy smokers, suggesting misclassification at high CPD or differences in inhalation and other smoking styles between heavy and light smokers (37-39). Accordingly, in epidemiological studies lung cancer risk has been shown to steadily increase up to 20-30 cigarettes per day, but plateau for subjects reporting CPD above 20-30 (38), Consistently, the excess ORs of lung cancer risk for each pack-year of exposure was shown to increase with increasing intensity of smoking only for subjects who smoke up to 20 cigarettes per day (33). We observed similar results in the current study, where
