Association between cardiorespiratory fitness and colorectal cancer in the UK Biobank

  • Andrea HillreinerEmail author
  • Sebastian E. Baumeister
  • Anja M. Sedlmeier
  • Jonas D. Finger
  • Hans J. Schlitt
  • Michael F. Leitzmann


Increased cardiorespiratory fitness is related to decreased risk of major chronic illnesses, including cardiovascular disease, type 2 diabetes, and cancer, but its association with colorectal cancer specifically has received very little attention. We examined the relation of cardiorespiratory fitness to colorectal cancer in 59,191 UK Biobank participants aged 39–70 years without prevalent cancer at baseline, followed from 2009 to 2014. Submaximal bicycle ergometry was conducted at study entry, and cardiorespiratory fitness was defined as physical work capacity at 75% of the maximum heart rate, standardised to body mass (PWC75%). Multivariable Cox proportional hazards regression was performed to obtain hazard ratios (HR) and corresponding 95% confidence intervals (CI). During a mean follow-up of 4.6 years, 232 participants developed colorectal cancer (151 colon cancers; 79 rectal cancers). When comparing the 75th to the 25th percentiles of PWC75%, the multivariable-adjusted HR of colorectal cancer was 0.78 (95% CI 0.62–0.97). That relation was largely driven by an inverse association with colon cancer (HR 0.74, 95% CI 0.56–0.97) and less so with rectal cancer (HR 0.88, 95% CI 0.62–1.26; p value for difference by colorectal cancer endpoint = 0.056). The inverse relation of cardiorespiratory fitness with colorectal cancer was more evident in men (HR 0.72, 95% CI 0.55–0.94) than women (HR 0.99, 95% CI 0.71–1.38), although the gender difference was not statistically significant (p value for interaction = 0.192). Increased cardiorespiratory fitness is associated with decreased risk of colorectal cancer. Potential heterogeneity by colorectal cancer anatomic subsite and gender requires further study.


Cardiorespiratory fitness Colorectal cancer Incidence UK Biobank Gender-specific 



Body mass index


Beats per minute


Confidence interval




Hazard ratio


International classification of diseases


International Physical Activity Questionnaire


Metabolic equivalent of task


North West Multi-centre Research Ethics Committee


Nonsteroidal anti-inflammatory drug


Physical work capacity at 75% of the maximum heart rate standardised to body mass



This research has been conducted using the UK Biobank Resource under Application Number 24091. The authors thank all study participants and the study personnel.

Authors contribution

AH conducted the data preparation and analysis. AH drafted the manuscript with support from ML and SB. ML and SB conceived the original idea and supervised the project. All authors directly participated in interpretation of the results, provided critical comments to the manuscript and revised the text. All authors of this research paper have read and approved the final version submitted.


The UK Biobank was supported by the Wellcome Trust, Medical Research Council, Department of Health, Scottish government, and Northwest Regional Development Agency. It has also had funding from the Welsh Assembly government and British Heart Foundation. The research was designed, conducted, analysed, and interpreted by the authors entirely independently of the funding sources.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed were in accordance and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and ethical approval was obtained from North West Multi-centre Research Ethics Committee (REC reference: 11/NW/03820).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10654_2019_575_MOESM1_ESM.docx (195 kb)
Supplementary material 1 (DOCX 196 kb)


  1. 1.
    Mahmood S, MacInnis RJ, English DR, Karahalios A, Lynch BM. Domain-specific physical activity and sedentary behaviour in relation to colon and rectal cancer risk: a systematic review and meta-analysis. Int J Epidemiol. 2017;46(6):1797–813. Scholar
  2. 2.
    Moore SC, Lee IM, Weiderpass E, Campbell PT, Sampson JN, Kitahara CM, et al. Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults. JAMA Int Med. 2016;176(6):816–25. Scholar
  3. 3.
    Vainshelboim B, Muller J, Lima RM, Nead KT, Chester C, Chan K, et al. Cardiorespiratory fitness and cancer incidence in men. Ann Epidemiol. 2017;27(7):442–7. Scholar
  4. 4.
    Robsahm TE, Falk RS, Heir T, Sandvik L, Vos L, Erikssen J, et al. Cardiorespiratory fitness and risk of site-specific cancers: a long-term prospective cohort study. Cancer Med. 2017;6(4):865–73. Scholar
  5. 5.
    Laukkanen JA, Pukkala E, Rauramaa R, Makikallio TH, Toriola AT, Kurl S. Cardiorespiratory fitness, lifestyle factors and cancer risk and mortality in Finnish men. Eur J Cancer (Oxford, England: 1990). 2010;46(2):355–63. Scholar
  6. 6.
    Lakoski SG, Willis BL, Barlow CE, Leonard D, Gao A, Radford NB, et al. Midlife cardiorespiratory fitness, incident cancer, and survival after cancer in men: the Cooper center longitudinal study. JAMA Oncol. 2015;1(2):231–7. Scholar
  7. 7.
    Steell L, Ho FK, Sillars A, Petermann-Rocha F, Li H, Lyall DM, et al. Dose-response associations of cardiorespiratory fitness with all-cause mortality and incidence and mortality of cancer and cardiovascular and respiratory diseases: the UK Biobank cohort study. Br J Sports Med. 2019. Scholar
  8. 8.
    Nunez C, Clausen J, Jensen MT, Holtermann A, Gyntelberg F, Bauman A. Main and interactive effects of physical activity, fitness and body mass in the prevention of cancer from the Copenhagen Male Study. Sci Rep. 2018;8(1):11780. Scholar
  9. 9.
    Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep. 1985;100(2):126–31.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Ross R, Blair SN, Arena R, Church TS, Despres JP, Franklin BA, et al. Importance of assessing cardiorespiratory fitness in clinical practice: a case for fitness as a clinical vital sign: a scientific statement from the American Heart Association. Circulation. 2016;134(24):e653–99. Scholar
  11. 11.
    Blair SN, Cheng Y, Holder JS. Is physical activity or physical fitness more important in defining health benefits? Med Sci Sports Exerc. 2001;33(6):S379–99 (discussion S419-20).CrossRefGoogle Scholar
  12. 12.
    McGuire KA, Ross R. Incidental physical activity is positively associated with cardiorespiratory fitness. Med Sci Sports Exerc. 2011;43(11):2189–94. Scholar
  13. 13.
    Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, et al. Colorectal cancer. Nat Rev Dis Prim. 2015;1:15065. Scholar
  14. 14.
    Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383(9927):1490–502. Scholar
  15. 15.
    Trehearne A. Genetics, lifestyle and environment UK Biobank is an open access resource following the lives of 500,000 participants to improve the health of future generations. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2016;59(3):361–7. Scholar
  16. 16.
    UK Biobank. Cardio Assessment. Version 1.0. 2011.
  17. 17.
    Noonan V, Dean E. Submaximal exercise testing: clinical application and interpretation. Phys Ther. 2000;80(8):782–807.PubMedGoogle Scholar
  18. 18.
    Eng JJ, Dawson AS, Chu KS. Submaximal exercise in persons with stroke: test-retest reliability and concurrent validity with maximal oxygen consumption. Arch Phys Med Rehabil. 2004;85(1):113–8.CrossRefGoogle Scholar
  19. 19.
    Gore CJ, Booth ML, Bauman A, Owen N. Utility of pwc75% as an estimate of aerobic power in epidemiological and population-based studies. Med Sci Sports Exerc. 1999;31(2):348–51.CrossRefGoogle Scholar
  20. 20.
    Hollmann W, Strüder H, Predel H-G, Tagarakis C. Spiroergometrie. Schattauer: Kardiopulmonale Leistungsdiagnostik des Gesunden und Kranken; 2006.Google Scholar
  21. 21.
    Batcho CS, Thonnard JL, Nielens H. PWC 75%/kg, a fitness index not linked to resting heart rate: testing procedure and reference values. Arch Phys Med Rehabil. 2012;93(7):1196–200. Scholar
  22. 22.
    Finger J, Gößwald A, Härtel S, Müters S, Krug S, Hölling H, et al. Measurement of cardiorespiratory fitness in the German Health Interview and Examination Survey for Adults (DEGS1). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2013;56(5–6):885–93. Scholar
  23. 23.
    Finger J, Krug S, Gößwald A, Härtel S, Bös K. Cardiorespiratory fitness among adults in Germany. Epidemiologie und Gesundheitsberichterstattung: Robert Koch-Institut; 2013.Google Scholar
  24. 24.
    Baumeister SE, Ricci C, Kohler S, Fischer B, Topfer C, Finger JD, et al. Physical activity surveillance in the European Union: reliability and validity of the European Health Interview Survey-Physical Activity Questionnaire (EHIS-PAQ). Int J Behav Nutr Phys Act. 2016;13:61. Scholar
  25. 25.
    Niedermann K, Sidelnikov E, Muggli C, Dagfinrud H, Hermann M, Tamborrini G, et al. Effect of cardiovascular training on fitness and perceived disease activity in people with ankylosing spondylitis. Arthritis Care Res. 2013;65(11):1844–52. Scholar
  26. 26.
    Nagashima J, Musha H, Takada H, Takagi K, Mita T, Mochida T, et al. Three-month exercise and weight loss program improves heart rate recovery in obese persons along with cardiopulmonary function. J Cardiol. 2010;56(1):79–84. Scholar
  27. 27.
    Tanaka H, Monahan KD, Seals DR. Age-predicted maximal heart rate revisited. J Am Coll Cardiol. 2001;37(1):153–6.CrossRefGoogle Scholar
  28. 28.
    Reifman A, Winsorize KK. In: Salkind NJ, editor. Encyclopedia of research design. Thousand Oaks: Sage; 2010. p. 1636–8.Google Scholar
  29. 29.
    World Health Organization (WHO). ICD-9: international statistical classification of diseases and related health problems/World Health Organization. Geneva: World Health Organization; 1978.Google Scholar
  30. 30.
    World Health Organization (WHO). ICD-10: international statistical classification of diseases and related health problems/World Health Organization. Geneva: World Health Organization; 2004.Google Scholar
  31. 31.
    VanderWeele TJ, Shpitser I. A new criterion for confounder selection. Biometrics. 2011;67(4):1406–13. Scholar
  32. 32.
    Textor J, van der Zander B, Gilthorpe MS, Liśkiewicz M, Ellison GTH. Robust causal inference using directed acyclic graphs: the R package ‘dagitty’. Int J Epidemiol. 2016;45(6):1887–94. Scholar
  33. 33.
    Hernán MA, Robins JM. Causal inference. Boca Raton: Chapman & Hall/CRC; 2019 (forthcoming).Google Scholar
  34. 34.
    Harrell FE. Regression modeling strategies: with applications to linear models, logistic and ordinal regression, and survival analysis. New York: Springer; 2015.CrossRefGoogle Scholar
  35. 35.
    van Buuren S, Groothuis-Oudshoorn K. Mice: multivariate imputation by chained equations in R. J Stat Softw. 2011;45(3):1–67. Scholar
  36. 36.
    Wang M, Spiegelman D, Kuchiba A, Lochhead P, Kim S, Chan AT, et al. Statistical methods for studying disease subtype heterogeneity. Stat Med. 2016;35(5):782–800. Scholar
  37. 37.
    VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the e-value. Ann Intern Med. 2017;167(4):268–74. Scholar
  38. 38.
    Haneuse S, VanderWeele TJ, Arterburn D. Using the E-value to assess the potential effect of unmeasured confounding in observational studies. JAMA. 2019;321(6):602–3. Scholar
  39. 39.
    McKinney J, Lithwick DJ, Morrison BN, Nazzari H, Isserow S, Heilbron B, et al. The health benefits of physical activity and cardiorespiratory fitness. BCMJ. 2016;58(3):131–7.Google Scholar
  40. 40.
    R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2016.Google Scholar
  41. 41.
    Pozuelo-Carrascosa DP, Alvarez-Bueno C, Cavero-Redondo I, Morais S, Lee IM, Martínez-Vizcaíno V. Cardiorespiratory fitness and site-specific risk of cancer in men: a systematic review and meta-analysis. Eur J Cancer. 2019;113:58–68. Scholar
  42. 42.
    American College of Sports Medicine. ACSM’s Guidelines for Exercise Testing and Prescription. 9th Edition. edn. Baltimore: Wolters Kluwer Health/Lippinoctt, Williams & Wilkins; 2014.Google Scholar
  43. 43.
    Lee S, Bacha F, Gungor N, Arslanian SA. Cardiorespiratory fitness in youth: relationship to insulin sensitivity and beta-cell function. Obesity (Silver Spring, Md). 2006;14(9):1579–85. Scholar
  44. 44.
    Vella CA, Van Guilder GP, Dalleck LC. Low cardiorespiratory fitness is associated with markers of insulin resistance in young, normal weight, hispanic women. Metab Syndr Relat Disord. 2016;14(5):272–8. Scholar
  45. 45.
    Santos RV, Viana VA, Boscolo RA, Marques VG, Santana MG, Lira FS, et al. Moderate exercise training modulates cytokine profile and sleep in elderly people. Cytokine. 2012;60(3):731–5. Scholar
  46. 46.
    Estaki M, Pither J, Baumeister P, Little JP, Gill SK, Ghosh S, et al. Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions. Microbiome. 2016;4(1):42. Scholar
  47. 47.
    Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, Shi J, et al. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst. 2013;105(24):1907–11. Scholar
  48. 48.
    Traustadottir T, Davies SS, Su Y, Choi L, Brown-Borg HM, Roberts LJ 2nd, et al. Oxidative stress in older adults: effects of physical fitness. Age (Dordrecht, Netherlands). 2012;34(4):969–82. Scholar
  49. 49.
    Missiaglia E, Jacobs B, D’Ario G, Di Narzo AF, Soneson C, Budinska E, et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol Off J Eur Soc Med Oncol. 2014;25(10):1995–2001. Scholar
  50. 50.
    Song M, Hu FB, Spiegelman D, Chan AT, Wu K, Ogino S, et al. Long-term status and change of body fat distribution, and risk of colorectal cancer: a prospective cohort study. Int J Epidemiol. 2016;45(3):871–83. Scholar
  51. 51.
    Murphy N, Strickler HD, Stanczyk FZ, Xue X, Wassertheil-Smoller S, Rohan TE, et al. A prospective evaluation of endogenous sex hormone levels and colorectal cancer risk in postmenopausal women. J Natl Cancer Inst. 2015;107(10):djv210. Scholar
  52. 52.
    Limsui D, Vierkant RA, Tillmans LS, Wang AH, Weisenberger DJ, Laird PW, et al. Postmenopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes among older women. Gut. 2012;61(9):1299–305. Scholar
  53. 53.
    Tarp J, Stole AP, Blond K, Grontved A. Cardiorespiratory fitness, muscular strength and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetologia. 2019;62(7):1129–42. Scholar
  54. 54.
    Guraya SY. Association of type 2 diabetes mellitus and the risk of colorectal cancer: a meta-analysis and systematic review. World J Gastroenterol. 2015;21(19):6026–31. Scholar
  55. 55.
    Jackson AS, Sui X, Hebert JR, Church TS, Blair SN. Role of lifestyle and aging on the longitudinal change in cardiorespiratory fitness. Arch Intern Med. 2009;169(19):1781–7. Scholar
  56. 56.
    Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc. 2011;43(7):1334–59. Scholar
  57. 57.
    Physical Activity Guidelines Advisory Committee. 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Washington, DC: U.S. Department of Health and Human Services; 2018.Google Scholar
  58. 58.
    Rezende LFM, Sa TH, Markozannes G, Rey-Lopez JP, Lee IM, Tsilidis KK, et al. Physical activity and cancer: an umbrella review of the literature including 22 major anatomical sites and 770,000 cancer cases. Br J Sports Med. 2018;52(13):826–33. Scholar
  59. 59.
    DeFina LF, Haskell WL, Willis BL, Barlow CE, Finley CE, Levine BD, et al. Physical activity versus cardiorespiratory fitness: two (partly) distinct components of cardiovascular health? Prog Cardiovasc Dis. 2015;57(4):324–9. Scholar
  60. 60.
    Williams PT. Physical fitness and activity as separate heart disease risk factors: a meta-analysis. Med Sci Sports Exerc. 2001;33(5):754–61. Scholar
  61. 61.
    Prince SA, Adamo KB, Hamel ME, Hardt J, Connor Gorber S, Tremblay M. A comparison of direct versus self-report measures for assessing physical activity in adults: a systematic review. Int J Behav Nutr Phys Act. 2008;5:56. Scholar
  62. 62.
    Button KS, Ioannidis JPA, Mokrysz C, Nosek BA, Flint J, Robinson ESJ, et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci. 2013;14:365. Scholar
  63. 63.
    Ioannidis JP. Why most discovered true associations are inflated. Epidemiology (Cambridge, MA). 2008;19(5):640–8. Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Epidemiology and Preventive MedicineUniversity of RegensburgRegensburgGermany
  2. 2.Chair of Epidemiology, LMU MünchenUNIKA-T AugsburgAugsburgGermany
  3. 3.Independent Research Group Clinical Epidemiology, Helmholtz Zentrum MünchenGerman Research Center for Environmental HealthMunichGermany
  4. 4.Department of Epidemiology and Health MonitoringRobert Koch InstituteBerlinGermany
  5. 5.Department of SurgeryUniversity Hospital RegensburgRegensburgGermany

Personalised recommendations