Abstract
BACKGROUND: Biological age acceleration helps to identify the gap between an individual's actual aging level and chronological age. Whether biological age acceleration mediates the effect of lifestyle factors on the risk of digestive system cancers remains unclear. METHODS: In this population-based prospective cohort study, 80,848 UK Biobank participants without cancer at baseline were included. Biological age was assessed by Phenotypic age. The lifestyle factor components were selected mainly based on the cancer prevention recommendations proposed by the World Cancer Research Fund and the American Institute for Cancer Research. In addition, a Healthy Lifestyle Index was calculated. With digestive system cancers as the outcome, Cox proportional hazards models were used to identify risk factors, and mediation analyses were conducted using biological age acceleration as the mediator. RESULTS: During a median follow-up of 13.8 years, 1957 cases of digestive system cancers were documented. Increased Phenotypic age acceleration (HR 1.03, 95% CI 1.02-1.04) was linked to higher risk of digestive system cancers. Phenotypic age acceleration mediated the effects of current smoking [Total natural indirect effect (TNIE) 1.04, 95% CI 1.03-1.06, proportion mediated (PM) 9.69%], middle (TNIE 1.03, 95% CI 1.02-1.04, PM 9.67%) and high waist circumference (TNIE 1.07, 95% CI 1.04-1.10, PM 18.30%), and Healthy Lifestyle Index (TNIE 0.97, 95% CI 0.97-0.98, PM 16.45%) on digestive system cancers. CONCLUSIONS: Our study illustrated that accelerated aging was a risk factor for digestive system cancers and mediated the effects of certain lifestyle factors on the risk of digestive system cancers and their subtypes, independent of chronological age.