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

Eleanor L. Watts; Paul A. Townsend; 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-Jarai; Fredrick R. Schumacher; Sara Benlloch; Ali Amin Al Olama; Kenneth R. Muir; Sonja I. Berndt; David V. Conti; Fredrik Wiklund; 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; 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

doi:10.1038/s41416-023-02489-3

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

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

Eleanor L. Watts, Paul A. Townsend, Tomas I. Gonzales, Tessa Strain, Pedro F. Saint-Maurice, D. Timothy Bishop, Stephen J. Chanock, Mattias Johansson, Temitope O. Keku, Loic Le Marchand, …

British journal of cancer

2023

DOI: https://doi.org/10.1038/s41416-023-02489-3

Abstract

Cancer and Oncology

Cancer och onkologi

Klinisk medicin

Medical and Health Sciences

Medicin och hälsovetenskap

Clinical Medicine

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.

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Title: Observational and genetic associations between cardiorespiratory fitness and cancer
Creators: Eleanor L. Watts - National Cancer Institute
Paul A. Townsend
Tomas I. Gonzales - MRC Epidemiology Unit
Tessa Strain - MRC Epidemiology Unit
Pedro F. Saint-Maurice - National Institutes of Health
D. Timothy Bishop - University of Leeds
Stephen J. Chanock - National Cancer Institute
Mattias Johansson - Centre International de Recherche sur le Cancer
Temitope O. Keku - University of North Carolina at Chapel Hill
Loic Le Marchand - University of Hawaii System
Victor Moreno - Universitat de Barcelona
Polly A. Newcomb - University of Washington
Christina C. Newton - American Cancer Society
Rish K. Pai - Mayo Clinic in Arizona
Mark P. Purdue - National Cancer Institute
Cornelia M. Ulrich - Huntsman Cancer Institute
Karl Smith-Byrne - University of Oxford
Bethany van Guelpen - Umeå University
Rosalind A. Eeles
Christopher A. Haiman - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, CA, Los Angeles, United States
Zsofia Kote-Jarai - The Institute of Cancer Research, London, United Kingdom
Fredrick R. Schumacher
Sara Benlloch
Ali Amin Al Olama
Kenneth R. Muir - University of Manchester
Sonja I. Berndt - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, MD, Bethesda, United States
David V. Conti - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, CA, Los Angeles, United States
Fredrik Wiklund - Karolinska Institutet
Stephen J. Chanock - National Cancer Institute
Ying Wang - Williams
Catherine M. Tangen - Fred Hutch Cancer Center
Jyotsna Batra
Judith A. Clements
Henrik Grönberg - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, MD, Bethesda, United States
Nora Pashayan
Johanna Schleutker
Demetrius Albanes - National Institutes of Health
Stephanie J. Weinstein - National Institutes of Health
Alicja Wolk - Uppsala University
Catharine M. L. West - University of Manchester
Lorelei A. Mucci - Department of Epidemiology, Harvard T. H. Chan School of Public Health, MA, Boston, United States
Géraldine Cancel-Tassin
Stella Koutros - National Institutes of Health
Karina Dalsgaard Sørensen
Eli Marie Grindedal - Oslo University Hospital
David E. Neal
Freddie C. Hamdy
Jenny L. Donovan - University of Bristol
Ruth C. Travis - University of Oxford
Robert J. Hamilton
Sue Ann Ingles - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, CA, Los Angeles, United States
Barry S. Rosenstein - Icahn School of Medicine at Mount Sinai
Yong-Jie Lu - Queen Mary University of London
Graham G. Giles
Robert J. MacInnis
Adam S. Kibel - Brigham and Women's Hospital
Ana Vega
Manolis Kogevinas
Kathryn L. Penney - Brigham and Women's Hospital
Jong Y. Park - Moffitt Cancer Center
Janet L. Stanford
Cezary Cybulski - Pomeranian Medical University
Børge G. Nordestgaard
Sune F. Nielsen
Hermann Brenner
Christiane Maier - Humangenetik Tuebingen, Paul-Ehrlich-Str 23, Tuebingen, Germany
Jeri Kim - The University of Texas M. D. Anderson Cancer Center, Department of Genitourinary Medical Oncology, 1515 Holcombe Blvd., TX, Houston, United States
Esther M. John - Stanford University School of Medicine
Manuel R. Teixeira
Susan L. Neuhausen - City of Hope
Kim De Ruyck - Ghent University
Azad Razack - Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
Lisa F. Newcomb - University of Washington
Davor Lessel - University Medical Center Hamburg-Eppendorf
Radka Kaneva - Medical University of Sofia
Nawaid Usmani
Frank Claessens - KU Leuven
Jose Esteban Castelao - Complexo Hospitalario Universitario A Coruña
Monique J. Roobol - Erasmus MC
Florence Menegaux - Inserm
Kay-Tee Khaw - University of Cambridge
Lisa Cannon-Albright
Hardev Pandha - University of Surrey
Stephen N. Thibodeau - Mayo Clinic in Arizona
David J. Hunter - University of Oxford
Peter Kraft - Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, MA, Boston, United States
William J. Blot
Elio Riboli - Imperial College London
Felix R. Day - University of Cambridge
Katrien Wijndaele - MRC Epidemiology Unit
Nicholas J. Wareham - University of Cambridge
Charles E. Matthews - National Cancer Institute
Steven C. Moore - National Cancer Institute
Soren Brage - University of Cambridge
Publication Details: British journal of cancer
Date published: 2023
Identifiers: 99843884302346
Academic Unit: FHMS Central Faculty Admin; Faculty of Health and Medical Sciences
Language: English
Resource Type: Journal article

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

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