Abstract B75: Aspirin use, body mass index, physical activity, plasma C-peptide, and colon cancer risk in U.S. health professionals
Authors: Zhang Xuehong , Smith-Warner Stephanie A. , Chan Andrew T. , Wu Kana , Spiegelman Donna , Willett Walter C. , Giovannucci Edward L. 
Published: January 2011

Abstract
Background: Aspirin use, especially at high dosage and long duration, decreases colon cancer risk but widespread aspirin use for preventing colon cancer is not recommended for individuals at average risk of colon cancer due to its associated side effects. However, particular subgroups at higher risk of colon cancer may benefit more from aspirin use. Limited epidemiological studies have investigated the aspirin-colon cancer association within these subgroups to date.
Objective: We investigated prospectively whether the aspirin-colon cancer association was stronger among three groups at increased risk of colon cancer: obese participants; physically inactive participants; or participants with higher levels of plasma C-peptide. We examined the aspirin association by these risk factors because they may affect colon cancer risk via similar underlying pathways.
Design: We evaluated the aspirin-colon cancer association according to body mass index (BMI) and physical activity in 1,701 incident colon cancer cases diagnosed during follow-up of 139,350 participants for up to 26 years in 2 prospective cohort studies. We estimated multivariable study-specific relative risks (RRs) and 95% confidence intervals (CIs) using a Cox proportional hazards model and pooled the results using a random effects model. We used a logistic regression model to analyze whether plasma C-peptide level modified the aspirin-colon cancer association using a nested case-control design (n=384 cases, 749 controls). We tested for multiplicative interactions by including a cross-product term for aspirin use and the potential effect modifier to evaluate whether the relative benefit of aspirin use on colon cancer risk was the same across lower and higher risk groups. We conducted additive interaction analyses by calculating the synergy index to evaluate whether the absolute reduction in colon cancer risk differed across lower and higher risk subgroups.
Results: Regular aspirin use was significantly associated with a 28% (95% CI: 20%-35%) lower risk of colon cancer compared to non-regular use. A dose-response relation was observed for both higher dosage and longer duration of use (tests for trend, P-value &lt;0.001). BMI did not modify the association between aspirin use and colon cancer risk; pooled multivariable RRs for regular aspirin use vs. nonuse were 0.74 (95% CI: 0.63-0.87) in the normal weight and 0.75 (95% CI: 0.60-0.93) in the obese groups (test for multiplicative interaction, P-value=0.75; test for additive interaction, P-value=0.66). Pooled multivariable RRs for regular aspirin use vs nonuse were 0.86 (95% CI: 0.66-1.11) in the low and 0.67 (95% CI: 0.58-0.77) in the high physical activity groups with no interaction evident on the multiplicative (P-value = 0.47) or additive (P-value = 0.11) scale. Plasma C-peptide also did not modify the aspirin-colon cancer association (multivariable RR=0.74; 95%CI: 0.50-1.10 for low, RR=0.65; 95%CI: 0.46-0.92 for high group, test for multiplicative interaction, P-value=0.55; test for additive interaction, P-value=0.38).
Conclusions: Reductions in colon cancer risk associated with aspirin use were not significantly modified by BMI, physical activity or plasma C-peptide level in this study. More studies are warranted to confirm these findings and to continue identifying subgroups of individuals who may benefit more from aspirin use.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B75.