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; Felix R Day; Katrien Wijndaele; Nicholas J Wareham; Charles E Matthews; Steven C Moore; Soren Brage; PRACTICAL consortium, CRUK, BPC3, CAPS, PEGASUS

doi:10.1038/s41416-023-02489-3

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, Felix R Day, Katrien Wijndaele, Nicholas J WarehamCharles E Matthews, Steven C Moore, Soren Brage, PRACTICAL consortium, CRUK, BPC3, CAPS, PEGASUS

Department of Clinical Biochemistry

6 Citations (Scopus)

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 language	English
Journal	British Journal of Cancer
Volume	130
Issue number	1
Pages (from-to)	114-124
Number of pages	11
ISSN	0007-0920
DOIs	https://doi.org/10.1038/s41416-023-02489-3
Publication status	Published - Jan 2024

Keywords

Male
Humans
Cardiorespiratory Fitness
Biological Specimen Banks
UK Biobank
Breast Neoplasms/epidemiology
Colorectal Neoplasms/epidemiology
Risk Factors

Access to Document

10.1038/s41416-023-02489-3

Cite this

Watts, E. L., Gonzales, T. I., Strain, T., Saint-Maurice, P. F., Bishop, D. T., Chanock, S. J., Johansson, M., Keku, T. O., Le Marchand, L., Moreno, V., Newcomb, P. A., Newton, C. C., Pai, R. K., Purdue, M. P., Ulrich, C. M., Smith-Byrne, K., Van Guelpen, B., Day, F. R., Wijndaele, K., ... PRACTICAL consortium, CRUK, BPC3, CAPS, PEGASUS (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. https://doi.org/10.1038/s41416-023-02489-3

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 & PRACTICAL consortium, CRUK, BPC3, CAPS, PEGASUS 2024, 'Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study', British Journal of Cancer, vol. 130, no. 1, pp. 114-124. https://doi.org/10.1038/s41416-023-02489-3

@article{ae098ebd08eb48159a251318094e0f0a,

title = "Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study",

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.",

keywords = "Male, Humans, Cardiorespiratory Fitness, Biological Specimen Banks, UK Biobank, Breast Neoplasms/epidemiology, Colorectal Neoplasms/epidemiology, Risk Factors",

author = "Watts, \{Eleanor L\} and Gonzales, \{Tomas I\} and Tessa Strain and Saint-Maurice, \{Pedro F\} and Bishop, \{D Timothy\} and Chanock, \{Stephen J\} and Mattias Johansson and Keku, \{Temitope O\} and \{Le Marchand\}, Loic and Victor Moreno and Newcomb, \{Polly A\} and Newton, \{Christina C\} and Pai, \{Rish K\} and Purdue, \{Mark P\} and Ulrich, \{Cornelia M\} and Karl Smith-Byrne and \{Van Guelpen\}, Bethany and Day, \{Felix R\} and Katrien Wijndaele and Wareham, \{Nicholas J\} and Matthews, \{Charles E\} and Moore, \{Steven C\} and Soren Brage and Nordestgaard, \{B{\o}rge G.\} and Nielsen, \{Sune Fallgaard\} and \{PRACTICAL consortium, CRUK, BPC3, CAPS, PEGASUS\}",

note = "{\textcopyright} 2023. The Author(s).",

year = "2024",

month = jan,

doi = "10.1038/s41416-023-02489-3",

language = "English",

volume = "130",

pages = "114--124",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Observational and genetic associations between cardiorespiratory fitness and cancer

T2 - a UK Biobank and international consortia study

AU - Watts, Eleanor L

AU - Gonzales, Tomas I

AU - Strain, Tessa

AU - Saint-Maurice, Pedro F

AU - Bishop, D Timothy

AU - Chanock, Stephen J

AU - Johansson, Mattias

AU - Keku, Temitope O

AU - Le Marchand, Loic

AU - Moreno, Victor

AU - Newcomb, Polly A

AU - Newton, Christina C

AU - Pai, Rish K

AU - Purdue, Mark P

AU - Ulrich, Cornelia M

AU - Smith-Byrne, Karl

AU - Van Guelpen, Bethany

AU - Day, Felix R

AU - Wijndaele, Katrien

AU - Wareham, Nicholas J

AU - Matthews, Charles E

AU - Moore, Steven C

AU - Brage, Soren

AU - PRACTICAL consortium, CRUK, BPC3, CAPS, PEGASUS

A2 - Nordestgaard, Børge G.

A2 - Nielsen, Sune Fallgaard

PY - 2024/1

Y1 - 2024/1

N2 - 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.

AB - 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.

KW - Male

KW - Humans

KW - Cardiorespiratory Fitness

KW - Biological Specimen Banks

KW - UK Biobank

KW - Breast Neoplasms/epidemiology

KW - Colorectal Neoplasms/epidemiology

KW - Risk Factors

UR - https://www.scopus.com/pages/publications/85178876689

U2 - 10.1038/s41416-023-02489-3

DO - 10.1038/s41416-023-02489-3

M3 - Journal article

C2 - 38057395

SN - 0007-0920

VL - 130

SP - 114

EP - 124

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 1

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this