Exercise Improves Cancer-free Survival and Health Span in a Model of Radiation-induced Cancer
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INTRODUCTION: Radiation therapy increases the risk of secondary malignancy and morbidity in cancer survivors. The role of obesity and exercise training in modulating this risk is not well-understood. As such, we used a preclinical model of radiation-induced malignancy to investigate whether diet-induced obesity and/or endurance exercise training altered life-long survival, cancer incidence, and morbidity. METHODS: Male CBA mice were randomly divided into control diet/sedentary group (CTRL/SED), high fat diet (45% fat)/sedentary group (HFD/SED), control diet/exercise group (2-3 days/week; CTRL/EX), or high fat diet/exercise group (HFD/EX) groups, then exposed to whole-body radiation (3 Gy). Endpoint monitoring and pathology determined mortality and cancer incidence, respectively. Healthspan index, a measure of morbidity, was determined by a composite measure of ten anthropometric, metabolic, performance, and behavioral measures. RESULTS: Overall survival was higher in HFD/SED compared to CTRL/SED (p < 0.05). Risk of cancer-related mortality by 18 months post-radiation was 1.99 and 1.63 in HFD/SED compared to CTRL/EX (RR = 1.99; 95% CI, 1.20-3.31; p = 0.0081) and CTRL/SED (RR = 1.63; 95% CI, 1.06-2.49; p = 0.0250), respectively. The number of mice at endpoint with cancer was higher in HFD/SED compared to CTRL/EX and CTRL/SED (p < 0.05). Healthspan index was highest in CTRL/EX (score = +2.5), followed by HFD/EX (score = +1), and HFD/SED (score = -1) relative to CTRL/SED. CONCLUSION: This work provides the basis for future preclinical studies investigating the dose-response relationship between exercise training and late effects of radiation therapy as well as the mechanisms responsible for these effects.
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