Body Weight, Physical Activity, and Risk of Cancer in Lynch Syndrome

SIMPLE SUMMARY: Lifestyle modifies cancer risk in the general public. How lifestyle modifies cancer risk in individuals carrying the inherited pathogenic gene variants in DNA mismatch repair genes (Lynch syndrome) remains understudied. We conducted a retrospective study with cancer register data to investigate associations between body weight, physical activity, and cancer risk among Finnish Lynch syndrome carriers (n = 465, 54% women). The results of our study indicated that longitudinal weight gain increases cancer risk, whereas being highly physically active during adulthood could decrease cancer risk in men. Further, women were observed to be less prone to lifestyle-related risk factors than men. The results emphasize the role of weight maintenance and high-intensity physical activity throughout the lifespan, especially in men with Lynch syndrome. ABSTRACT: Lynch syndrome (LS) increases cancer risk. There is considerable individual variation in LS cancer occurrence, which may be moderated by lifestyle factors, such as body weight and physical activity (PA). The potential associations of lifestyle and cancer risk in LS are understudied. We conducted a retrospective study with cancer register data to investigate associations between body weight, PA, and cancer risk among Finnish LS carriers. The participants (n = 465, 54% women) self-reported their adulthood body weight and PA at 10-year intervals. Overall cancer risk and colorectal cancer (CRC) risk was analyzed separately for men and women with respect to longitudinal and near-term changes in body weight and PA using extended Cox regression models. The longitudinal weight change was associated with an increased risk of all cancers (HR 1.02, 95% CI 1.00–1.04) and CRC (HR 1.03, 1.01–1.05) in men. The near-term weight change was associated with a lower CRC risk in women (HR 0.96, 0.92–0.99). Furthermore, 77.6% of the participants retained their PA category over time. Men in the high-activity group had a reduced longitudinal cancer risk of 63% (HR 0.37, 0.15–0.98) compared to men in the low-activity group. PA in adulthood was not associated with cancer risk among women. These results emphasize the role of weight maintenance and high-intensity PA throughout the lifespan in cancer prevention, particularly in men with LS.