We conducted a cohort study of alcohol consumption and total cancer incidence and mortality in 73,281 subjects (35,007 men and 38,274 women) aged 40-59 years old at baseline over a 10-year follow-up period. During 1990-2001, a total of 3403 cases of newly diagnosed cancer and 1208 cancer deaths were identified. In men, the lowest risk of developing cancer was observed among occasional drinkers, and a linear positive association with increased ethanol intake was noted (hazard ratio 1.18 for 1-149 g per week, 1.17 for 150-299 g per week, 1.43 for 300-449 g per week, 1.61 for > or = 450 g per week, P for trend < 0.001). The positive relation was similar for cancer incidence and mortality, but was more striking among current smokers and alcohol-related cancers. Relatively few women were regular drinkers. Our results suggest that increased ethanol intake linearly elevates the risk of cancer, and that nearly 13% of cancers among males in this study were due to heavy drinking (> or = 300 g per week of ethanol), to which smoking substantially contributed. The simultaneous reduction of smoking is therefore important for reducing the effect of alcohol on cancer risk.