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

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ICR Authors

Eeles, Rosalind
 Kote-Jarai, Zsofia

Authors

Watts, EL
Gonzales, TI
Strain, T
Saint-Maurice, PF
Bishop, DT
Chanock, SJ
Johansson, M
Keku, TO
Le Marchand, L
Moreno, V
Newcomb, PA
Newton, CC
Pai, RK
Purdue, MP
Ulrich, CM
Smith-Byrne, K
Van Guelpen, B
Day, FR
Wijndaele, K
Wareham, NJ
Matthews, CE
Moore, SC
Brage, S
Eeles, RA
Haiman, CA
Kote-Jarai, Z
Schumacher, FR
Benlloch, S
Al Olama, AA
Muir, KR
Berndt, SI
Conti, DV
Wiklund, F
Chanock, SJ
Wang, Y
Tangen, CM
Batra, J
Clements, JA
Gronberg, H
Pashayan, N
Schleutker, J
Albanes, D
Weinstein, SJ
Wolk, A
West, CML
Mucci, LA
Cancel-Tassin, G
Koutros, S
Sorensen, KD
Grindedal, EM
Neal, DE
Hamdy, FC
Donovan, JL
Travis, RC
Hamilton, RJ
Ingles, SA
Rosenstein, BS
Lu, Y-J
Giles, GG
MacInnis, RJ
Kibel, AS
Vega, A
Kogevinas, M
Penney, KL
Park, JY
Stanford, JL
Cybulski, C
Nordestgaard, BG
Nielsen, SF
Brenner, H
Maier, C
Kim, J
John, EM
Teixeira, MR
Neuhausen, SL
De Ruyck, K
Razack, A
Newcomb, LF
Lessel, D
Kaneva, R
Usmani, N
Claessens, F
Townsend, PA
Esteban Castelao, J
Roobol, MJ
Menegaux, F
Khaw, K-T
Cannon-Albright, L
Pandha, H
Thibodeau, SN
Hunter, DJ
Kraft, P
Blot, WJ
Riboli, E

Document Type

Journal Article

Date

2024-01-31

Date Accepted

2023-10-31

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>The association of fitness with cancer risk is not clear.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p> 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 ( <jats:italic>N</jats:italic>  = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. </jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O <jats:sub>2</jats:sub> ⋅min <jats:sup>−1</jats:sup> ⋅kg <jats:sup>−1</jats:sup> 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 <jats:sub>2</jats:sub> ⋅min <jats:sup>−1</jats:sup> ⋅kg <jats:sup>−1</jats:sup> 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. </jats:p> </jats:sec> <jats:sec> <jats:title>Discussion</jats:title> <jats:p>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.</jats:p> </jats:sec>

Citation

British Journal of Cancer, 2024, 130 (1),

DOI

10.1038/s41416-023-02489-3
10.1038/s41416-023-02489-3

URI

https://repository.icr.ac.uk/handle/internal/6233

Rights

http://creativecommons.org/licenses/by/4.0/

Source Title

British Journal of Cancer

Publisher

SPRINGERNATURE

ISSN

0007-0920

eISSN

1532-1827
1532-1827

Collections

Genetics and Epidemiology

Research Team

Oncogenetics

Notes