Healthy Lifestyle Factors Associated With Lower Risk of Colorectal Cancer Irrespective of Genetic Risk

Background & Aims: The combined effects of healthy lifestyle factors on colorectal cancer (CRC) risk are unclear. We aimed to develop a healthy lifestyle score, to investigate the joint effects of modifiable lifestyle factors on reduction of CRC risk and determine whether associations differ with genetic risk. Methods: We collected data from a large population-based case-control study in Germany and used multiple logistic regression analyses to examine associations between the healthy lifestyle score (derived from 5 modifiable lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body fatness) and CRC risk. We created a genetic risk score, based on 53 risk variants, to investigate the association of the healthy lifestyle score and risk of CRC, stratified by genetic risk. Results: We included 4092 patients with CRC and 3032 individuals without CRC (controls) in our analysis. In adjusted models, compared with participants with 0 or 1 healthy lifestyle factor, participants with 2 (odds ratio [OR] 0.85; 95% confidence interval [CI] 0.67–1.06), 3 (OR 0.62; 95% CI 0.50–0.77), 4 (OR 0.53; 95% CI 0.42–0.66), or 5 (OR 0.33; 95% CI 0.26–0.43) healthy lifestyle factors had increasingly lower risks of CRC (P trend <.0001). We found no differences among subgroups stratified by genetic risk score, history of colonoscopy, or family history of CRC. Overall, 45% of CRC cases (95% CI 34%–53%) could be attributed to nonadherence to all 5 healthy lifestyle behaviors. Conclusions: In a large population-based case-control study, we identified a combination of lifestyle factors that appears to reduce risk of CRC, regardless of the patient's genetic profile. These results reinforce the importance of primary prevention of CRC.