Observational and genetic associations between cardiorespiratory fitness and cancer: A UK Biobank and international consortia study

Eleanor L. Watts, Tomas I. Gonzales, Tessa Strain, Pedro F. Saint-Maurice, D. Timothy Bishop, Stephen J. Chanock, Mattias Johansson, Temitope O. Keku, Loic Le Marchand, Victor Moreno, Polly Newcomb, Christina C. Newton, Rish K. Pai, Mark P. Purdue, Cornelia M. Ulrich, Karl Smith-Byrne, Bethany Van Guelpen, The PRACTICAL consortium, CRUK, BPC3, CAPS, PEGASUS, Felix R Day, Katrien WijndaeleNicholas J. Wareham, Charles E. Matthews, Steven C. Moore, Soren Brage

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background: The association of fitness with cancer risk is not clear. 

Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. 

Results: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O 2⋅min −1⋅kg −1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O 2⋅min −1⋅kg −1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. 

Discussion: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.

Original languageEnglish
Pages (from-to)114-124
Number of pages11
JournalBritish Journal of Cancer
Volume130
Early online date6 Dec 2023
DOIs
Publication statusPublished - 31 Jan 2024

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