Meta-analyses of colorectal cancer risk factors Constance M. JohnsonCaimiao WeiJoe E. Ensor • Derek J. SmolenskiChristopher I. AmosBernard Levin •

Purpose Demographic, behavioral, and environmental factors have been associated with increased risk of colorectal cancer (CRC). We reviewed the published evidence and explored associations between risk factors and CRC incidence. Methods We identified 12 established non-screening CRC risk factors and performed a comprehensive review and meta-analyses to quantify each factor’s impact on CRC risk. We used random-effects models of the logarithms of risks across studies: inverse-variance weighted averages for dichotomous factors and generalized least squares for dose‐response for multi-level factors. Results Significant risk factors include inflammatory bowel disease (RR = 2.93, 95 % CI 1.79‐4.81); CRC history in first-degree relative (RR = 1.80, 95 % CI 1.61‐2.02); body mass index (BMI) to overall population (RR = 1.10 per 8 kg/m 2 increase, 95 % CI 1.08‐1.12); physical activity (RR = 0.88, 95 % CI 0.86‐0.91 for 2 standard deviations increased physical activity score); cigarette smoking (RR = 1.06, 95 % CI 1.03‐1.08 for 5 pack-years); and consumption of red meat (RR = 1.13, 95 % CI 1.09‐1.16 for 5 servings/week), fruit (RR = 0.85, 95 % CI 0.75‐0.96 for 3 servings/day), and vegetables (RR = 0.86, 95 % CI 0.78‐0.94 for 5 servings/day). Conclusions We developed a comprehensive risk modeling strategy that incorporates multiple effects to predict an individual’s risk of developing CRC. Inflammatory bowel disease and history of CRC in first-degree relatives are associated with much higher risk of CRC. Increased BMI, red meat intake, cigarette smoking, low physical activity, low vegetable consumption, and low fruit consumption were associated with moderately increased risk of CRC.