Observational and genetic associations between cardiorespiratory fitness and cancer: A UK Biobank and international consortia study
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 c...
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RD Surgery Watts, Eleanor L. Gonzales, Tomas I. Strain, Tessa Saint-Maurice, Pedro F. Bishop, D. Timothy Chanock, Stephen J. Johansson, Mattias Keku, Temitope O. Le Marchand, Loic Moreno, Victor Newcomb, Polly A. Newton, Christina C. Pai, Rish K. Purdue, Mark P. Ulrich, Cornelia M. Smith-Byrne, Karl Van Guelpen, Bethany Eeles, Rosalind A. Haiman, Christopher A. Kote-Jarai, Zsofia Schumacher, Fredrick R. Benlloch, Sara Olama, Ali Amin Al Muir, Kenneth R. Berndt, Sonja I. Conti, David V. Wiklund, Fredrik Wang, Ying Tangen, Catherine M. Batra, Jyotsna Clements, Judith A. Grönberg, Henrik Pashayan, Nora Schleutker, Johanna Albanes, Demetrius Weinstein, Stephanie J. Wolk, Alicja West, Catharine M. L. Mucci, Lorelei A. Cancel-Tassin, Géraldine Koutros, Stella Sørensen, Karina Dalsgaard Grindedal, Eli Marie Neal, David E. Hamdy, Freddie C. Donovan, Jenny L. Travis, Ruth C. Hamilton, Robert J. Ingles, Sue Ann Rosenstein, Barry S. Lu, Yong-Jie Giles, Graham G. MacInnis, Robert J. Kibel, Adam S. Vega, Ana Kogevinas, Manolis Penney, Kathryn L. Park, Jong Y. Stanford, Janet L. Cybulski, Cezary Nordestgaard, Børge G. Nielsen, Sune F. Brenner, Hermann Maier, Christiane Kim, Jeri John, Esther M. Teixeira, Manuel R. Neuhausen, Susan L. De Ruyck, Kim Abdul Razack, Azad Hassan Newcomb, Lisa F. Lessel, Davor Kaneva, Radka Usmani, Nawaid Claessens, Frank Townsend, Paul A. Castelao, Jose Esteban Roobol, Monique J. Menegaux, Florence Khaw, Kay-Tee Cannon-Albright, Lisa Pandha, Hardev Thibodeau, Stephen N. Hunter, David J. Kraft, Peter Blot, William J. Riboli, Elio Day, Felix R. Wijndaele, Katrien Wareham, Nicholas J. Matthews, Charles E. Moore, Steven C. Brage, Soren Observational and genetic associations between cardiorespiratory fitness and cancer: A UK Biobank and international consortia study |
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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). |
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Watts, Eleanor L. Gonzales, Tomas I. Strain, Tessa Saint-Maurice, Pedro F. Bishop, D. Timothy Chanock, Stephen J. Johansson, Mattias Keku, Temitope O. Le Marchand, Loic Moreno, Victor Newcomb, Polly A. Newton, Christina C. Pai, Rish K. Purdue, Mark P. Ulrich, Cornelia M. Smith-Byrne, Karl Van Guelpen, Bethany Eeles, Rosalind A. Haiman, Christopher A. Kote-Jarai, Zsofia Schumacher, Fredrick R. Benlloch, Sara Olama, Ali Amin Al Muir, Kenneth R. Berndt, Sonja I. Conti, David V. Wiklund, Fredrik Wang, Ying Tangen, Catherine M. Batra, Jyotsna Clements, Judith A. Grönberg, Henrik Pashayan, Nora Schleutker, Johanna Albanes, Demetrius Weinstein, Stephanie J. Wolk, Alicja West, Catharine M. L. Mucci, Lorelei A. Cancel-Tassin, Géraldine Koutros, Stella Sørensen, Karina Dalsgaard Grindedal, Eli Marie Neal, David E. Hamdy, Freddie C. Donovan, Jenny L. Travis, Ruth C. Hamilton, Robert J. Ingles, Sue Ann Rosenstein, Barry S. Lu, Yong-Jie Giles, Graham G. MacInnis, Robert J. Kibel, Adam S. Vega, Ana Kogevinas, Manolis Penney, Kathryn L. Park, Jong Y. Stanford, Janet L. Cybulski, Cezary Nordestgaard, Børge G. Nielsen, Sune F. Brenner, Hermann Maier, Christiane Kim, Jeri John, Esther M. Teixeira, Manuel R. Neuhausen, Susan L. De Ruyck, Kim Abdul Razack, Azad Hassan Newcomb, Lisa F. Lessel, Davor Kaneva, Radka Usmani, Nawaid Claessens, Frank Townsend, Paul A. Castelao, Jose Esteban Roobol, Monique J. Menegaux, Florence Khaw, Kay-Tee Cannon-Albright, Lisa Pandha, Hardev Thibodeau, Stephen N. Hunter, David J. Kraft, Peter Blot, William J. Riboli, Elio Day, Felix R. Wijndaele, Katrien Wareham, Nicholas J. Matthews, Charles E. Moore, Steven C. Brage, Soren |
author_facet |
Watts, Eleanor L. Gonzales, Tomas I. Strain, Tessa Saint-Maurice, Pedro F. Bishop, D. Timothy Chanock, Stephen J. Johansson, Mattias Keku, Temitope O. Le Marchand, Loic Moreno, Victor Newcomb, Polly A. Newton, Christina C. Pai, Rish K. Purdue, Mark P. Ulrich, Cornelia M. Smith-Byrne, Karl Van Guelpen, Bethany Eeles, Rosalind A. Haiman, Christopher A. Kote-Jarai, Zsofia Schumacher, Fredrick R. Benlloch, Sara Olama, Ali Amin Al Muir, Kenneth R. Berndt, Sonja I. Conti, David V. Wiklund, Fredrik Wang, Ying Tangen, Catherine M. Batra, Jyotsna Clements, Judith A. Grönberg, Henrik Pashayan, Nora Schleutker, Johanna Albanes, Demetrius Weinstein, Stephanie J. Wolk, Alicja West, Catharine M. L. Mucci, Lorelei A. Cancel-Tassin, Géraldine Koutros, Stella Sørensen, Karina Dalsgaard Grindedal, Eli Marie Neal, David E. Hamdy, Freddie C. Donovan, Jenny L. Travis, Ruth C. Hamilton, Robert J. Ingles, Sue Ann Rosenstein, Barry S. Lu, Yong-Jie Giles, Graham G. MacInnis, Robert J. Kibel, Adam S. Vega, Ana Kogevinas, Manolis Penney, Kathryn L. Park, Jong Y. Stanford, Janet L. Cybulski, Cezary Nordestgaard, Børge G. Nielsen, Sune F. Brenner, Hermann Maier, Christiane Kim, Jeri John, Esther M. Teixeira, Manuel R. Neuhausen, Susan L. De Ruyck, Kim Abdul Razack, Azad Hassan Newcomb, Lisa F. Lessel, Davor Kaneva, Radka Usmani, Nawaid Claessens, Frank Townsend, Paul A. Castelao, Jose Esteban Roobol, Monique J. Menegaux, Florence Khaw, Kay-Tee Cannon-Albright, Lisa Pandha, Hardev Thibodeau, Stephen N. Hunter, David J. Kraft, Peter Blot, William J. Riboli, Elio Day, Felix R. Wijndaele, Katrien Wareham, Nicholas J. Matthews, Charles E. Moore, Steven C. Brage, Soren |
author_sort |
Watts, Eleanor L. |
title |
Observational and genetic associations between cardiorespiratory fitness and cancer: A UK Biobank and international consortia study |
title_short |
Observational and genetic associations between cardiorespiratory fitness and cancer: A UK Biobank and international consortia study |
title_full |
Observational and genetic associations between cardiorespiratory fitness and cancer: A UK Biobank and international consortia study |
title_fullStr |
Observational and genetic associations between cardiorespiratory fitness and cancer: A UK Biobank and international consortia study |
title_full_unstemmed |
Observational and genetic associations between cardiorespiratory fitness and cancer: A UK Biobank and international consortia study |
title_sort |
observational and genetic associations between cardiorespiratory fitness and cancer: a uk biobank and international consortia study |
publisher |
Springer Nature |
publishDate |
2024 |
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http://eprints.um.edu.my/44877/ |
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1805881179523514368 |
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my.um.eprints.448772024-06-14T03:10:54Z http://eprints.um.edu.my/44877/ Observational and genetic associations between cardiorespiratory fitness and cancer: A UK Biobank and international consortia study Watts, Eleanor L. Gonzales, Tomas I. Strain, Tessa Saint-Maurice, Pedro F. Bishop, D. Timothy Chanock, Stephen J. Johansson, Mattias Keku, Temitope O. Le Marchand, Loic Moreno, Victor Newcomb, Polly A. Newton, Christina C. Pai, Rish K. Purdue, Mark P. Ulrich, Cornelia M. Smith-Byrne, Karl Van Guelpen, Bethany Eeles, Rosalind A. Haiman, Christopher A. Kote-Jarai, Zsofia Schumacher, Fredrick R. Benlloch, Sara Olama, Ali Amin Al Muir, Kenneth R. Berndt, Sonja I. Conti, David V. Wiklund, Fredrik Wang, Ying Tangen, Catherine M. Batra, Jyotsna Clements, Judith A. Grönberg, Henrik Pashayan, Nora Schleutker, Johanna Albanes, Demetrius Weinstein, Stephanie J. Wolk, Alicja West, Catharine M. L. Mucci, Lorelei A. Cancel-Tassin, Géraldine Koutros, Stella Sørensen, Karina Dalsgaard Grindedal, Eli Marie Neal, David E. Hamdy, Freddie C. Donovan, Jenny L. Travis, Ruth C. Hamilton, Robert J. Ingles, Sue Ann Rosenstein, Barry S. Lu, Yong-Jie Giles, Graham G. MacInnis, Robert J. Kibel, Adam S. Vega, Ana Kogevinas, Manolis Penney, Kathryn L. Park, Jong Y. Stanford, Janet L. Cybulski, Cezary Nordestgaard, Børge G. Nielsen, Sune F. Brenner, Hermann Maier, Christiane Kim, Jeri John, Esther M. Teixeira, Manuel R. Neuhausen, Susan L. De Ruyck, Kim Abdul Razack, Azad Hassan Newcomb, Lisa F. Lessel, Davor Kaneva, Radka Usmani, Nawaid Claessens, Frank Townsend, Paul A. Castelao, Jose Esteban Roobol, Monique J. Menegaux, Florence Khaw, Kay-Tee Cannon-Albright, Lisa Pandha, Hardev Thibodeau, Stephen N. Hunter, David J. Kraft, Peter Blot, William J. Riboli, Elio Day, Felix R. Wijndaele, Katrien Wareham, Nicholas J. Matthews, Charles E. Moore, Steven C. Brage, Soren RD Surgery 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). Springer Nature 2024 Article PeerReviewed 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 <https://doi.org/10.1038/s41416-023-02489-3>. 10.1038/s41416-023-02489-3 |