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 A. Newcomb, Christina C. Newton, Rish K. Pai, Mark P. Purdue, Cornelia M. Ulrich, Karl Smith-Byrne, Bethany Van Guelpen, Rosalind A. Eeles, Christopher A. Haiman, Zsofia Kote-JaraiFredrick R. Schumacher, Sara Benlloch, Ali Amin Al Olama, Kenneth R. Muir, Sonja I. Berndt, David V. Conti, Fredrik Wiklund, Stephen J. Chanock, Ying Wang, Catherine M. Tangen, Jyotsna Batra, Judith A. Clements, Henrik Grönberg, Nora Pashayan, Johanna Schleutker, Demetrius Albanes, Stephanie J. Weinstein, Alicja Wolk, Catharine M.L. West, Lorelei A. Mucci, Géraldine Cancel-Tassin, Stella Koutros, Karina Dalsgaard Sørensen, Eli Marie Grindedal, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Ruth C. Travis, Robert J. Hamilton, Sue Ann Ingles, Barry S. Rosenstein, Yong Jie Lu, Graham G. Giles, Robert J. MacInnis, Adam S. Kibel, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Jong Y. Park, Janet L. Stanford, Cezary Cybulski, Børge G. Nordestgaard, Sune F. Nielsen, Hermann Brenner, Christiane Maier, Jeri Kim, Esther M. John, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Razack, Lisa F. Newcomb, Davor Lessel, Radka Kaneva, Nawaid Usmani, Frank Claessens, Paul A. Townsend, Jose Esteban Castelao, Monique J. Roobol, Florence Menegaux, Kay Tee Khaw, Lisa Cannon-Albright, Hardev Pandha, Stephen N. Thibodeau, David J. Hunter, Peter Kraft, William J. Blot, Elio Riboli, Felix R. Day, Katrien Wijndaele, Nicholas J. Wareham, Charles E. Matthews, Steven C. Moore, Soren Brage*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Abstract

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 O2⋅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 O2⋅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
Issue number1
DOIs
Publication statusPublished - 31 Jan 2024

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

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