Cigarette smoking and cancer: Intensity patterns in the alpha-tocopherol, beta-carotene cancer prevention study in Finnish men

Relative risks for lung and bladder cancers by smoking intensity level off at more than 15-20 cigarettes per day. A three-parameter excess relative risk model in pack-years and intensity quantified this leveling (Lubin et al., Am J Epidemiol 2007;166:479-89). Above 15-20 cigarettes per day was an "inverse exposure rate" effect whereby, for equal pack-years, the excess relative risk/pack-year decreased with increasing intensity; that is, smoking at a lower intensity for a longer duration was more deleterious than smoking at a higher intensity for a shorter duration. After adjustment for pack-years, intensity effects were quantitatively homogeneous across multiple case-control studies of lung, bladder, oral cavity, pancreas, and esophagus cancers. The authors extended those analyses to examine intensity patterns for incident bladder, esophagus, kidney, larynx, liver, lung, oropharynx, and pancreas cancers by using data from a single prospective cohort in Finland, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, with follow-up from enrollment, which occurred between 1985 and 1988, through April 2004. At more than 10 cigarettes per day, they found an inverse exposure rate pattern for each cancer site. After adjustment for pack-years, intensity effects were quantitatively homogeneous across the diverse cancer sites and homogeneous with intensity effects from the prior analysis of multiple studies. Consistency of intensity patterns suggested a general phenomenon and may provide clues to the molecular basis of smoking-related cancer risk.