Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study
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Date
2024-01-31Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
<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>
Collections
Subject
Science & Technology
Life Sciences & Biomedicine
Oncology
MENDELIAN RANDOMIZATION ANALYSES
GENOME-WIDE ASSOCIATION
ALL-CAUSE MORTALITY
SUSCEPTIBILITY LOCI
RISK
ADIPOSITY
OBESITY
INSTRUMENTS
MEN
Research team
Oncogenetics
Language
eng
Date accepted
2023-10-31
License start date
2024-01-31
Citation
British Journal of Cancer, 2024, 130 (1),
Publisher
SPRINGERNATURE