PURPOSE: Based on suggestive findings from a recent study of high-risk Japanese 
patients, we sought to determine whether the risk of colorectal polyps 
associated with smoking may be modified by daily use of aspirin in an analysis 
of a large US screening population.
METHODS: This is a cross-sectional study of 2,918 consecutive colonoscopy 
patients at a university hospital over a 30-month period. Data were abstracted 
from electronic medical records. Multivariate models of polyp counts were used 
to examine the competing risks of smoking and aspirin use. Models were further 
stratified by polyp location (proximal vs. distal) and pathologic subtype 
(dysplastic vs. serrated).
RESULTS: Incidental rate of polyps was higher among active smokers [incidence 
rate ratio (IRR) 1.72; 95 % confidence interval (CI) 1.46-2.02] and lower among 
daily aspirin users (IRR 0.73; 95 % CI 0.61-0.86) compared to those who used 
neither. Smoking interacts significantly with aspirin use resulting in loss of 
aspirin protection (IRR 1.69; 95 % CI 1.28-2.24). Stratified analyses 
demonstrate that aspirin specifically reduces the risk of traditional dysplastic 
adenomas (IRR 0.72; 95 % CI 0.61-0.86) not serrated/hyperplastic polyps (IRR 
0.92; 95 % CI 0.72-1.17) and that the modification of aspirin protection by 
smoking is primarily observed within the distal colorectum (p < 0.03).
CONCLUSIONS: We report for the first time, in a typical risk US clinical 
population, a lack of protective association of aspirin for polyps among active 
smokers. Future prospective studies are recommended to confirm this mitigating 
effect in order to improve the precision of the growing evidence base about the 
chemopreventive benefit of aspirin in colorectal cancer.