An estimated two-thirds of cancer deaths in the U.S. can be attributed to modifiable risk factors such as smoking, diet and exercise. Exercise has been shown to exert anti-tumor effects, including the reduction of incidence of cancer, to provide benefit as adjunct therapy during cancer treatment and to improve clinical outcomes by decreasing recurrence and mortality when occurring after diagnosis. While exercise is the strongest positive modifiable risk factor, surprisingly, the molecular mechanisms by which it influences cancer evolution are still almost entirely unknown. To address this gap in knowledge, we aim to enhance the molecular understanding of exercise oncology by precisely identifying clinical and molecular features associated with exercise. We will characterize the effects of exercise on cancer mutational and evolutionary processes (Aim 1), assess host biomarker responses to exercise (Aim 2), and evaluate the role of genetics and dose-dependent exercise interactions in cancer-related outcomes (Aim 3). The UKBB is a unique resource that provides physical activity measurements, genomic profiling, and clinical outcomes for a large cohort of human individuals. Exercise therapy has significant public health potential due to its accessibility, safety, cost effectiveness and ability to give individuals agency to positively influence their own risk of cancer or clinical outcomes. We hope our work will reveal important insights into the mechanisms by why exercise affects cancer and viability of prescribing exercise therapy as a preventative, adjunct and treatment strategy.
