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; 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; Stephen J. Chanock; 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; Paul A. Townsend; 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

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, Rosalind A. Eeles, Christopher A. Haiman, Zsofia Kote-JaraiFredrick R. Schumacher, Sara Benlloch, Ali Amin Al Olama, Kenneth R. Muir, Sonja I. Berndt, David V. Conti, Fredrik Wiklund, Stephen J. Chanock, 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, Paul A. Townsend, 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

Research output: Contribution to journal › Article › peer-review

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 (US)
Pages (from-to)	114-124
Number of pages	11
Journal	British journal of cancer
Volume	130
Issue number	1
DOIs	https://doi.org/10.1038/s41416-023-02489-3
State	Published - Jan 31 2024

ASJC Scopus subject areas

Oncology
Cancer Research

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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., Eeles, R. A., Haiman, C. A., ... Brage, S. (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, Eeles, RA, Haiman, CA, Kote-Jarai, Z, Schumacher, FR, Benlloch, S, Olama, AAA, Muir, KR, Berndt, SI, Conti, DV, Wiklund, F, Chanock, SJ, Wang, Y, Tangen, CM, Batra, J, Clements, JA, Grönberg, H, Pashayan, N, Schleutker, J, Albanes, D, Weinstein, SJ, Wolk, A, West, CML, Mucci, LA, Cancel-Tassin, G, Koutros, S, Sørensen, KD, Grindedal, EM, Neal, DE, Hamdy, FC, Donovan, JL, Travis, RC, Hamilton, RJ, Ingles, SA, Rosenstein, BS, Lu, YJ, 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, Castelao, JE, Roobol, MJ, Menegaux, F, Khaw, KT, Cannon-Albright, L, Pandha, H, Thibodeau, SN, Hunter, DJ, Kraft, P, Blot, WJ, Riboli, E, Day, FR, Wijndaele, K, Wareham, NJ, Matthews, CE, Moore, SC & Brage, S 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

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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.",

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 Eeles, {Rosalind A.} and Haiman, {Christopher A.} and Zsofia Kote-Jarai and Schumacher, {Fredrick R.} and Sara Benlloch and Olama, {Ali Amin Al} and Muir, {Kenneth R.} and Berndt, {Sonja I.} and Conti, {David V.} and Fredrik Wiklund and Chanock, {Stephen J.} and Ying Wang and Tangen, {Catherine M.} and Jyotsna Batra and Clements, {Judith A.} and Henrik Gr{\"o}nberg and Nora Pashayan and Johanna Schleutker and Demetrius Albanes and Weinstein, {Stephanie J.} and Alicja Wolk and West, {Catharine M.L.} and Mucci, {Lorelei A.} and G{\'e}raldine Cancel-Tassin and Stella Koutros and S{\o}rensen, {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 Ana Vega and Manolis Kogevinas and Penney, {Kathryn L.} and Park, {Jong Y.} and Stanford, {Janet L.} and Cezary Cybulski and Nordestgaard, {B{\o}rge G.} and Nielsen, {Sune F.} and Hermann Brenner and Christiane Maier and Jeri Kim and John, {Esther M.} and Teixeira, {Manuel R.} and Neuhausen, {Susan L.} and {De Ruyck}, Kim and Azad Razack and Newcomb, {Lisa F.} and Davor Lessel and Radka Kaneva and Nawaid Usmani and Frank Claessens and Townsend, {Paul A.} and Castelao, {Jose Esteban} and Roobol, {Monique J.} and Florence Menegaux and Khaw, {Kay Tee} and Lisa Cannon-Albright and Hardev Pandha and Thibodeau, {Stephen N.} and Hunter, {David J.} and Peter Kraft and Blot, {William J.} and Elio Riboli and Day, {Felix R.} and Katrien Wijndaele and Wareham, {Nicholas J.} and Matthews, {Charles E.} and Moore, {Steven C.} and Soren Brage",

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

year = "2024",

month = jan,

day = "31",

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

language = "English (US)",

volume = "130",

pages = "114--124",

journal = "British journal of cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "1",

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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 - Eeles, Rosalind A.

AU - Haiman, Christopher A.

AU - Kote-Jarai, Zsofia

AU - Schumacher, Fredrick R.

AU - Benlloch, Sara

AU - Olama, Ali Amin Al

AU - Muir, Kenneth R.

AU - Berndt, Sonja I.

AU - Conti, David V.

AU - Wiklund, Fredrik

AU - Chanock, Stephen J.

AU - Wang, Ying

AU - Tangen, Catherine M.

AU - Batra, Jyotsna

AU - Clements, Judith A.

AU - Grönberg, Henrik

AU - Pashayan, Nora

AU - Schleutker, Johanna

AU - Albanes, Demetrius

AU - Weinstein, Stephanie J.

AU - Wolk, Alicja

AU - West, Catharine M.L.

AU - Mucci, Lorelei A.

AU - Cancel-Tassin, Géraldine

AU - Koutros, Stella

AU - Sørensen, Karina Dalsgaard

AU - Grindedal, Eli Marie

AU - Neal, David E.

AU - Hamdy, Freddie C.

AU - Donovan, Jenny L.

AU - Travis, Ruth C.

AU - Hamilton, Robert J.

AU - Ingles, Sue Ann

AU - Rosenstein, Barry S.

AU - Lu, Yong Jie

AU - Giles, Graham G.

AU - MacInnis, Robert J.

AU - Kibel, Adam S.

AU - Vega, Ana

AU - Kogevinas, Manolis

AU - Penney, Kathryn L.

AU - Park, Jong Y.

AU - Stanford, Janet L.

AU - Cybulski, Cezary

AU - Nordestgaard, Børge G.

AU - Nielsen, Sune F.

AU - Brenner, Hermann

AU - Maier, Christiane

AU - Kim, Jeri

AU - John, Esther M.

AU - Teixeira, Manuel R.

AU - Neuhausen, Susan L.

AU - De Ruyck, Kim

AU - Razack, Azad

AU - Newcomb, Lisa F.

AU - Lessel, Davor

AU - Kaneva, Radka

AU - Usmani, Nawaid

AU - Claessens, Frank

AU - Townsend, Paul A.

AU - Castelao, Jose Esteban

AU - Roobol, Monique J.

AU - Menegaux, Florence

AU - Khaw, Kay Tee

AU - Cannon-Albright, Lisa

AU - Pandha, Hardev

AU - Thibodeau, Stephen N.

AU - Hunter, David J.

AU - Kraft, Peter

AU - Blot, William J.

AU - Riboli, Elio

AU - Day, Felix R.

AU - Wijndaele, Katrien

AU - Wareham, Nicholas J.

AU - Matthews, Charles E.

AU - Moore, Steven C.

AU - Brage, Soren

PY - 2024/1/31

Y1 - 2024/1/31

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.

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UR - http://www.scopus.com/inward/citedby.url?scp=85178876689&partnerID=8YFLogxK

U2 - 10.1038/s41416-023-02489-3

DO - 10.1038/s41416-023-02489-3

M3 - Article

C2 - 38057395

AN - SCOPUS:85178876689

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

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