Angiotensin I-converting enzyme gene polymorphism modifies the smoking-cancer association: the Hisayama Study

We examined the long-term contribution of smoking and angiotensin I-converting enzyme (ACE) gene I/D polymorphism to total cancer deaths in a prospective study of a general Japanese population. A total of 937 subjects aged 40 years or older were selected from an original cohort of 1621 subjects and were followed up for 32 years. During the follow-up period, 176 subjects died of cancer. Cancer mortality increased significantly with increasing current smoking levels. Although no clear relationship was observed between ACE genotypes and fatal cancer, the interaction term between current smoking and ACE genotype DD was found to be significant. In stratified analysis by ACE genotype after controlling for age, sex, alcohol intake, body mass index, glucose intolerance, serum total cholesterol and systolic blood pressure, the risk of fatal cancer in currently smoking subjects with genotype DD was twofold greater than that in subjects with genotypes II and ID. Among current smokers, subjects with genotype DD also showed a significantly greater risk of death due to cancer compared with those with genotypes II and ID combined (hazard ratio 1.77; 95% confidence interval 1.04-3.00; P=0.03). In conclusion, our findings suggest that ACE genotype DD enhances the association between smoking and cancer death in the general population.