Background: Across Europe, there are over 300,000 new cases of colorectal cancer annually. Major risk factors include excess body weight (usually expressed by a high body mass index, BMI) and physical inactivity (PA). In this study we modelled the potential long-term effects on colon cancer incidence of changes in prevalence of excess body weight and physical inactivity in seven European countries across Europe with adequate data. Methods: We addressed the impact of interventions aimed at preventing weight gain and increasing physical activity on colon cancer incidence using the Prevent model as refined in the FP-6 Eurocadet project. Relative risk (RR) estimates were derived from meta-analyses; sex- and country-specific prevalences of BMI and PA were determined from survey data. Models were made for Czech Republic, Denmark, France, Latvia, the Netherlands, Spain and the United Kingdom. Results: In a hypothetical scenario in which a whole population had obtained an ideal weight distribution in the year 2009, up to 11 new cases per 100,000 person-years would be avoided by 2040. The population attributable fractions (PAP) for excess weight were much higher for males (between 13.5% and 18.2%) than for females (2.3-4.6%). In contrast, using the optimum scenario where everybody in Europe would adhere to the recommended guideline of at least 30 min of moderate PA 5 d per week, the PAFs for PA in various countries were substantially greater in women (4.4-21.2%) than in men (3.2-11.6%). Sensitivity analyses were performed assuming underreporting of BMI by using self-reports (difference of 5 and 0.8 percent-points in males and females, respectively), using different risk estimates (between 5.8 and 11.5 percent-points difference for BMI for men and women, respectively, and up to 11.6 percent-points difference for PA for women). Interpretation: Changes in lifestyle can indeed result in large health benefits, including for colon cancer. Two interesting patterns emerged: for colon cancer, achieving optimum BM levels in the population appears to offer the greatest health benefits in population attributable fractions in males, while increased physical activity might offer the greatest fraction of avoidable cancers in females. These observations suggest a sex-specific strategy to colon cancer prevention. (C) 2010 Elsevier Ltd. All rights reserved.