Abstract
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.
Similar content being viewed by others
Availability of data and materials
UK Biobank is an open access resource. Bona fide researchers can apply to use the UK Biobank data set by registering and applying at http://www.ukbiobank.ac.uk/register-apply.
Abbreviations
- BMI:
-
Body mass index
- bpm:
-
Beats per minute
- CI:
-
Confidence interval
- ECG:
-
Electrocardiograph
- HR:
-
Hazard ratio
- ICD:
-
International classification of diseases
- IPAQ:
-
International Physical Activity Questionnaire
- MET:
-
Metabolic equivalent of task
- MREC:
-
North West Multi-centre Research Ethics Committee
- NSAID:
-
Nonsteroidal anti-inflammatory drug
- PWC75% :
-
Physical work capacity at 75% of the maximum heart rate standardised to body mass
References
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. https://doi.org/10.1093/ije/dyx137.
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. https://doi.org/10.1001/jamainternmed.2016.1548.
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. https://doi.org/10.1016/j.annepidem.2017.06.003.
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. https://doi.org/10.1002/cam4.1043.
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. https://doi.org/10.1016/j.ejca.2009.07.013.
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. https://doi.org/10.1001/jamaoncol.2015.0226.
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. https://doi.org/10.1136/bjsports-2018-099093.
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. https://doi.org/10.1038/s41598-018-30280-5.
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.
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. https://doi.org/10.1161/cir.0000000000000461.
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).
McGuire KA, Ross R. Incidental physical activity is positively associated with cardiorespiratory fitness. Med Sci Sports Exerc. 2011;43(11):2189–94. https://doi.org/10.1249/MSS.0b013e31821e4ff2.
Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, et al. Colorectal cancer. Nat Rev Dis Prim. 2015;1:15065. https://doi.org/10.1038/nrdp.2015.65.
Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383(9927):1490–502. https://doi.org/10.1016/S0140-6736(13)61649-9.
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. https://doi.org/10.1007/s00103-015-2297-0.
UK Biobank. Cardio Assessment. Version 1.0. 2011. https://biobank.ctsu.ox.ac.uk/crystal/docs/Cardio.pdf.
Noonan V, Dean E. Submaximal exercise testing: clinical application and interpretation. Phys Ther. 2000;80(8):782–807.
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.
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.
Hollmann W, Strüder H, Predel H-G, Tagarakis C. Spiroergometrie. Schattauer: Kardiopulmonale Leistungsdiagnostik des Gesunden und Kranken; 2006.
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. https://doi.org/10.1016/j.apmr.2012.02.021.
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. https://doi.org/10.1007/s00103-013-1694-5.
Finger J, Krug S, Gößwald A, Härtel S, Bös K. Cardiorespiratory fitness among adults in Germany. Epidemiologie und Gesundheitsberichterstattung: Robert Koch-Institut; 2013.
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. https://doi.org/10.1186/s12966-016-0386-6.
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. https://doi.org/10.1002/acr.22062.
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. https://doi.org/10.1016/j.jjcc.2010.03.001.
Tanaka H, Monahan KD, Seals DR. Age-predicted maximal heart rate revisited. J Am Coll Cardiol. 2001;37(1):153–6.
Reifman A, Winsorize KK. In: Salkind NJ, editor. Encyclopedia of research design. Thousand Oaks: Sage; 2010. p. 1636–8.
World Health Organization (WHO). ICD-9: international statistical classification of diseases and related health problems/World Health Organization. Geneva: World Health Organization; 1978.
World Health Organization (WHO). ICD-10: international statistical classification of diseases and related health problems/World Health Organization. Geneva: World Health Organization; 2004.
VanderWeele TJ, Shpitser I. A new criterion for confounder selection. Biometrics. 2011;67(4):1406–13. https://doi.org/10.1111/j.1541-0420.2011.01619.x.
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. https://doi.org/10.1093/ije/dyw341.
Hernán MA, Robins JM. Causal inference. Boca Raton: Chapman & Hall/CRC; 2019 (forthcoming).
Harrell FE. Regression modeling strategies: with applications to linear models, logistic and ordinal regression, and survival analysis. New York: Springer; 2015.
van Buuren S, Groothuis-Oudshoorn K. Mice: multivariate imputation by chained equations in R. J Stat Softw. 2011;45(3):1–67. https://doi.org/10.18637/jss.v045.i03.
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. https://doi.org/10.1002/sim.6793.
VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the e-value. Ann Intern Med. 2017;167(4):268–74. https://doi.org/10.7326/M16-2607.
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. https://doi.org/10.1001/jama.2018.21554.
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.
R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2016.
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. https://doi.org/10.1016/j.ejca.2019.03.008.
American College of Sports Medicine. ACSM’s Guidelines for Exercise Testing and Prescription. 9th Edition. edn. Baltimore: Wolters Kluwer Health/Lippinoctt, Williams & Wilkins; 2014.
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. https://doi.org/10.1038/oby.2006.182.
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. https://doi.org/10.1089/met.2015.0135.
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. https://doi.org/10.1016/j.cyto.2012.07.028.
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. https://doi.org/10.1186/s40168-016-0189-7.
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. https://doi.org/10.1093/jnci/djt300.
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. https://doi.org/10.1007/s11357-011-9277-6.
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. https://doi.org/10.1093/annonc/mdu275.
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. https://doi.org/10.1093/ije/dyv177.
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. https://doi.org/10.1093/jnci/djv210.
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. https://doi.org/10.1136/gutjnl-2011-300719.
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. https://doi.org/10.1007/s00125-019-4867-4.
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. https://doi.org/10.3748/wjg.v21.i19.6026.
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. https://doi.org/10.1001/archinternmed.2009.312.
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. https://doi.org/10.1249/mss.0b013e318213fefb.
Physical Activity Guidelines Advisory Committee. 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Washington, DC: U.S. Department of Health and Human Services; 2018.
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. https://doi.org/10.1136/bjsports-2017-098391.
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. https://doi.org/10.1016/j.pcad.2014.09.008.
Williams PT. Physical fitness and activity as separate heart disease risk factors: a meta-analysis. Med Sci Sports Exerc. 2001;33(5):754–61. https://doi.org/10.1097/00005768-200105000-00012.
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. https://doi.org/10.1186/1479-5868-5-56.
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. https://doi.org/10.1038/nrn3475.
Ioannidis JP. Why most discovered true associations are inflated. Epidemiology (Cambridge, MA). 2008;19(5):640–8. https://doi.org/10.1097/EDE.0b013e31818131e7.
Acknowledgement
This research has been conducted using the UK Biobank Resource under Application Number 24091. The authors thank all study participants and the study personnel.
Funding
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.
Author information
Authors and Affiliations
Contributions
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.
Corresponding author
Ethics declarations
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.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Hillreiner, A., Baumeister, S.E., Sedlmeier, A.M. et al. Association between cardiorespiratory fitness and colorectal cancer in the UK Biobank. Eur J Epidemiol 35, 961–973 (2020). https://doi.org/10.1007/s10654-019-00575-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10654-019-00575-6