Associations between smoking, passive smoking, GSTM-1, NAT2, and rectal cancer

Cigarette smoking has been identified as a risk factor for colon cancer, however, much less is known about the association between cigarette smoking and rectal cancer. The purpose of this article is to evaluate the associations between rectal cancer and active and passive cigarette smoking and other forms of tobacco use. We also evaluate how genetic variants of GSTM-1 and NAT2 alter these associations. A population-based case-control study of 952 incident rectal cancer cases and 1205 controls was conducted. Detailed tobacco use information was collected as part of an interviewer-administered questionnaire. DNA was extracted from blood to examine genetic variants of GSTM-1 and NAT2. Cigarette smoking was associated with an increased risk of rectal cancer in men [odds ratio (OR)=1.5, 95% confidence interval (CI), 1.1-2.1 for current smokers; OR=1.7, 95% CI, 1.3-2.3 for smoking >20 pack-years of cigarettes relative to never-smokers]. After adjusting for active smoking, exposure to cigarette smoke of others also was associated with increased risk among men (OR=1.5, 95% CI, 1.1-2.0). Neither GSTM-1 genotype nor NAT2-imputed phenotype was independently associated with rectal cancer. However, the risk associated with smoking cigarettes among those who were GSTM-1 null relative to those who never smoked and had the GSTM-1 present genotype was OR=2.0 (95% CI, 1.2-3.3). This interaction was of borderline significance (P=0.08). Men who had the combined GSTM-1 present genotype and who were rapid acetylators had no increased risk from cigarette smoking. There were no significant associations between cigarette smoking and rectal cancer among women. This study shows that men who smoke cigarettes, especially those who smoke >20 pack-years, are at increased risk of rectal cancer. This association may be influenced by GSTM-1 genotype. Furthermore, exposure to cigarette smoke of others may increase risk of rectal cancer among men who do not smoke.