Accelerometry-measured prolonged and interrupted sedentary behavior and cancer incidence and mortality: A cohort study of 91,292 UK Biobank participants

BACKGROUND: Current sedentary behavior (SB) guidelines primarily emphasize total time spent sedentary. We explored differences between interrupted and prolonged SB in relation to a range of cancer outcomes. METHODS AND FINDINGS: This study included 91,292 UK Biobank participants with valid accelerometer data. Participants were followed for a median of 12.38 years (interquartile range 11.56-13.15 years). A two-step approach based on a random forest model was used to classify SB. Multivariable Cox proportional hazards models were applied to overall incident cancers and cancer deaths, plus obesity-related and type-2 diabetes-related cancers, and 23 site-specific cancers. Models were adjusted for demographic, socioeconomic, lifestyle, dietary, and health-status factors, including age, ethnicity, deprivation, education, smoking, alcohol intake, diet, and morbidity count. Isotemporal substitution models were used to estimate the associated cancer risk when replacing prolonged SB with intermittent SB, or physical activity (PA). After adjusting for sociodemographic and lifestyle factors, each additional hour of prolonged SB was associated with a higher risk of overall cancer mortality (hazard ratio [HR] HR1hour 1.09; 95% confidence interval [CI] [1.06, 1.11]; p < 0.001). Replacing 1 hour per day of prolonged SB with light PA (HRLPA 0.88; 95% CI [0.79, 0.99]; p = 0.033) was associated with lower risk of overall cancer mortality. Similarly, replacing 30 min per day of prolonged SB with moderate PA (HRMPA 0.92; 95% CI [0.86, 0.99]; p = 0.024) was associated with a lower risk of overall cancer mortality. The main methodological limitations were observational design, residual confounding, healthy volunteer bias, and measurement imprecision due to having only 7 days of accelerometer wear. CONCLUSION: Cancer risk associated with SB is specific to prolonged SB. Replacing prolonged SB physical activity is associated with lower cancer risk.