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

Watts, Eleanor L. and Gonzales, Tomas I. and Strain, Tessa and Saint-Maurice, Pedro F. and Bishop, D. Timothy and Chanock, Stephen J. and Johansson, Mattias and Keku, Temitope O. and Le Marchand, Loic and Moreno, Victor and Newcomb, Polly A. and Newton, Christina C. and Pai, Rish K. and Purdue, Mark P. and Ulrich, Cornelia M. and Smith-Byrne, Karl and Van Guelpen, Bethany and Eeles, Rosalind A. and Haiman, Christopher A. and Kote-Jarai, Zsofia and Schumacher, Fredrick R. and Benlloch, Sara and Olama, Ali Amin Al and Muir, Kenneth R. and Berndt, Sonja I. and Conti, David V. and Wiklund, Fredrik and Wang, Ying and Tangen, Catherine M. and Batra, Jyotsna and Clements, Judith A. and Grönberg, Henrik and Pashayan, Nora and Schleutker, Johanna and Albanes, Demetrius and Weinstein, Stephanie J. and Wolk, Alicja and West, Catharine M. L. and Mucci, Lorelei A. and Cancel-Tassin, Géraldine and Koutros, Stella and Sørensen, Karina Dalsgaard and Grindedal, Eli Marie and Neal, David E. and Hamdy, Freddie C. and Donovan, Jenny L. and Travis, Ruth C. and Hamilton, Robert J. and Ingles, Sue Ann and Rosenstein, Barry S. and Lu, Yong-Jie and Giles, Graham G. and MacInnis, Robert J. and Kibel, Adam S. and Vega, Ana and Kogevinas, Manolis and Penney, Kathryn L. and Park, Jong Y. and Stanford, Janet L. and Cybulski, Cezary and Nordestgaard, Børge G. and Nielsen, Sune F. and Brenner, Hermann and Maier, Christiane and Kim, Jeri and John, Esther M. and Teixeira, Manuel R. and Neuhausen, Susan L. and De Ruyck, Kim and Abdul Razack, Azad Hassan and Newcomb, Lisa F. and Lessel, Davor and Kaneva, Radka and Usmani, Nawaid and Claessens, Frank and Townsend, Paul A. and Castelao, Jose Esteban and Roobol, Monique J. and Menegaux, Florence and Khaw, Kay-Tee and Cannon-Albright, Lisa and Pandha, Hardev and Thibodeau, Stephen N. and Hunter, David J. and Kraft, Peter and Blot, William J. and Riboli, Elio and Day, Felix R. and Wijndaele, Katrien and Wareham, Nicholas J. and Matthews, Charles E. and Moore, Steven C. and Brage, Soren (2024) Observational and genetic associations between cardiorespiratory fitness and cancer: A UK Biobank and international consortia study. British Journal of Cancer, 130 (1). 114 – 124. ISSN 0007-0920, DOI https://doi.org/10.1038/s41416-023-02489-3.

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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. © 2023, The Author(s).

Item Type: Article
Funders: ECAC, National Institutes of Health, British Columbia Arts Council, Medical Research Council [Grant no. MC_UU_00006/1, MC_UU_00006/2, MC_UU_00006/4], National Institute for Health and Care Research, University of Cambridge
Uncontrolled Keywords: Biological specimen banks; Breast neoplasms; Cardiorespiratory fitness; Colorectal neoplasms; Humans; Male; Risk factors; UK biobank; Article; biobank; Body mass; Breast cancer; Cancer prevention; Cancer risk; Cardiorespiratory fitness; Fat free mass; Female; Follow up; Genetic association; Genetic association study; Human; Major clinical study; Male; Malignant neoplasm; Mendelian randomization analysis; Metabolic equivalent; Obesity; Observational study; Proportional hazards model; Prostate cancer; Biobank; Breast tumor; Colorectal tumor; Genetics; Risk factor
Subjects: R Medicine > RD Surgery
Divisions: Faculty of Medicine > Surgery Department
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 14 Jun 2024 03:10
Last Modified: 14 Jun 2024 03:10
URI: http://eprints.um.edu.my/id/eprint/44877

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