Skip to main content

Advertisement

SpringerLink
Log in

Metabolic syndrome and the risk of colorectal cancer: a systematic review and meta-analysis

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Observational studies have reported an association between metabolic syndrome (MetS) and colorectal cancer risk with inconsistent risk estimates. We conducted this meta-analysis to evaluate the risk of colorectal cancer in individuals with MetS.

Methods

PubMed, Embase, and Web of Science were searched for related studies from database inception to 21 January 2021. Risk estimates for colorectal cancer were extracted from individual articles and pooled using a fixed-effect or random-effect model according to the heterogeneity.

Results

MetS was significantly associated with a higher risk of colorectal cancer in both sexes (relative risk [RR] 1.36, 95% confidence interval [CI] 1.26–1.47, P < 0.001), men (RR 1.33, 95% CI 1.21–1.47, P < 0.001), and women (RR 1.34, 95% CI 1.19–1.52, P < 0.001). The risk of colorectal cancer seemed to increase as the number of MetS components rose. Moreover, the high body mass index (BMI)/waist circumference (WC) and hyperglycemia were all significantly associated with a higher risk of colorectal cancer (RR 1.28 [1.20–1.37] and 1.31 [1.14–1.50] in both sexes, RR 1.31 [1.19–1.45] and 1.23 [1.03–1.46] in men, and RR 1.22 [1.02–1.46] and 1.63 [1.16–2.28] in women, respectively).

Conclusions

MetS was significantly associated with a higher risk of colorectal cancer. The high BMI/WC or hyperglycemia might largely account for this association. Further analysis suggested that, as the number of MetS components increased, the risk of colorectal cancer rose.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and material

All data generated or analyzed during this study are included in this published article.

References

  1. de Haas E, Oosting S, Lefrandt J et al (2010) The metabolic syndrome in cancer survivors. Lancet Oncol 11:193–203. https://doi.org/10.1016/s1470-2045(09)70287-6

    Article  PubMed  Google Scholar 

  2. Cornier M, Dabelea D, Hernandez T et al (2008) The metabolic syndrome. Endocr Rev 29:777–822. https://doi.org/10.1210/er.2008-0024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. O’Sullivan D, Sutherland R, Town S et al (2021) Risk factors for early-onset colorectal cancer: a systematic review and meta-analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. https://doi.org/10.1016/j.cgh.2021.01.037

    Article  Google Scholar 

  4. Moore J, Chaudhary N, Akinyemiju T (2017) Metabolic syndrome prevalence by race/ethnicity and sex in the United States, National Health and Nutrition Examination Survey, 1988–2012. Prev Chronic Dis 14:E24. https://doi.org/10.5888/pcd14.160287

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ma A, Fang K, Dong J, Dong Z (2020) Prevalence and related factors of metabolic syndrome in Beijing, China (Year 2017). Obes Facts 13:538–547. https://doi.org/10.1159/000508842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lovre D, Mauvais-Jarvis F (2015) Trends in prevalence of the metabolic syndrome. JAMA 314:950. https://doi.org/10.1001/jama.2015.8625

    Article  PubMed  Google Scholar 

  7. Zimmet P, Magliano D, Matsuzawa Y, Alberti G, Shaw J (2005) The metabolic syndrome: a global public health problem and a new definition. J Atheroscler Thromb 12:295–300. https://doi.org/10.5551/jat.12.295

    Article  CAS  PubMed  Google Scholar 

  8. Grundy S (2006) Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol 47:1093–1100. https://doi.org/10.1016/j.jacc.2005.11.046

    Article  CAS  PubMed  Google Scholar 

  9. Grundy S (2008) Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol 28:629–636. https://doi.org/10.1161/atvbaha.107.151092

    Article  CAS  PubMed  Google Scholar 

  10. Guize L, Thomas F, Pannier B et al (2007) All-cause mortality associated with specific combinations of the metabolic syndrome according to recent definitions. Diabetes Care 30:2381–2387. https://doi.org/10.2337/dc07-0186

    Article  CAS  PubMed  Google Scholar 

  11. Chen H, Zheng X, Zong X et al (2020) Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer. Gut. https://doi.org/10.1136/gutjnl-2020-321661

    Article  PubMed  Google Scholar 

  12. Pelucchi C, Negri E, Talamini R et al (2010) Metabolic syndrome is associated with colorectal cancer in men. Eur J Cancer 46:1866–1872. https://doi.org/10.1016/j.ejca.2010.03.010

    Article  PubMed  Google Scholar 

  13. Esposito K, Chiodini P, Colao A, Lenzi A, Giugliano D (2012) Metabolic syndrome and risk of cancer: a systematic review and meta-analysis. Diabetes Care 35:2402–2411. https://doi.org/10.2337/dc12-0336

    Article  PubMed  PubMed Central  Google Scholar 

  14. Esposito K, Chiodini P, Capuano A et al (2013) Colorectal cancer association with metabolic syndrome and its components: a systematic review with meta-analysis. Endocrine 44:634–647. https://doi.org/10.1007/s12020-013-9939-5

    Article  CAS  PubMed  Google Scholar 

  15. Harding J, Sooriyakumaran M, Anstey KJ et al (2015) The metabolic syndrome and cancer: Is the metabolic syndrome useful for predicting cancer risk above and beyond its individual components? Diabetes Metab 41:463–469. https://doi.org/10.1016/j.diabet.2015.04.006

    Article  CAS  PubMed  Google Scholar 

  16. Stürmer T, Buring JE, Lee IM, Gaziano JM, Glynn RJ (2006) Metabolic abnormalities and risk for colorectal cancer in the physicians’ health study. Cancer Epidemiol Biomarkers Prev 15:2391–2397. https://doi.org/10.1158/1055-9965.epi-06-0391

    Article  PubMed  PubMed Central  Google Scholar 

  17. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605. https://doi.org/10.1007/s10654-010-9491-z

    Article  PubMed  Google Scholar 

  18. Higgins J, Thompson S (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558. https://doi.org/10.1002/sim.1186

    Article  PubMed  Google Scholar 

  19. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285: 2486–2497. https://doi.org/10.1001/jama.285.19.2486

  20. Laaksonen D, Lakka H, Salonen J et al (2002) Low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome. Diabetes Care 25:1612–1618. https://doi.org/10.2337/diacare.25.9.1612

    Article  PubMed  Google Scholar 

  21. Grundy S, Brewer H, Cleeman J, Smith S, Lenfant C (2004) Definition of metabolic syndrome: report of the national heart, lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109:433–438. https://doi.org/10.1161/01.cir.0000111245.75752.c6

    Article  PubMed  Google Scholar 

  22. Alberti K, Zimmet P, Shaw J (2006) Metabolic syndrome–a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabetic medicine : a journal of the British Diabetic Association 23:469–480. https://doi.org/10.1111/j.1464-5491.2006.01858.x

    Article  CAS  Google Scholar 

  23. Lee J, Lee KS, Kim H et al (2020) The relationship between metabolic syndrome and the incidence of colorectal cancer. Environ Health Prev Med 25:6. https://doi.org/10.1186/s12199-020-00845-w

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kim J, Park EY, Park E et al (2020) Metabolic syndrome and colorectal cancer risk: results of propensity score-based analyses in a community-based cohort study. Int J Environ Res Public Health 17. https://doi.org/10.3390/ijerph17228687

  25. Milano A, Bianco MA, Buri L et al (2019) Metabolic syndrome is a risk factor for colorectal adenoma and cancer: a study in a White population using the harmonized criteria. Therap Adv Gastroenterol 12:1756284819867839. https://doi.org/10.1177/1756284819867839

    Article  PubMed  PubMed Central  Google Scholar 

  26. Li X, Chen H, Wang G et al (2019) Metabolic syndrome components and the risk of colorectal cancer: a population-based prospective study in Chinese Men. Front Oncol 9:1047. https://doi.org/10.3389/fonc.2019.01047

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ulaganathan V, Kandiah M, Mohd Shariff Z (2018) A case-control study of the association between metabolic syndrome and colorectal cancer: a comparison of International Diabetes Federation, National Cholesterol Education Program Adults Treatment Panel III, and World Health Organization definitions. J Gastrointest Oncol 9:650–663. https://doi.org/10.21037/jgo.2018.04.01

  28. Liang X, Margolis KL, Hendryx M et al (2017) Metabolic phenotype and risk of colorectal cancer in normal-weight postmenopausal women. Cancer Epidemiol Biomarkers Prev 26:155–161. https://doi.org/10.1158/1055-9965.epi-16-0761

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ko S, Yoon SJ, Kim D et al (2016) Metabolic risk profile and cancer in Korean men and women. J Prev Med Public Health 49:143–152. https://doi.org/10.3961/jpmph.16.021

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ulaganathan V, Kandiah M, Zalilah MS et al (2012) Colorectal cancer and its association with the metabolic syndrome: a Malaysian multi-centric case-control study. Asian Pac J Cancer Prev 13:3873–3877. https://doi.org/10.7314/apjcp.2012.13.8.3873

    Article  CAS  PubMed  Google Scholar 

  31. Osaki Y, Taniguchi S, Tahara A, Okamoto M, Kishimoto T (2012) Metabolic syndrome and incidence of liver and breast cancers in Japan. Cancer Epidemiol 36:141–147. https://doi.org/10.1016/j.canep.2011.03.007

    Article  PubMed  Google Scholar 

  32. Kabat GC, Kim MY, Peters U et al (2012) A longitudinal study of the metabolic syndrome and risk of colorectal cancer in postmenopausal women. Eur J Cancer Prev 21:326–332. https://doi.org/10.1097/CEJ.0b013e32834dbc81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Aleksandrova K, Boeing H, Jenab M et al (2011) Metabolic syndrome and risks of colon and rectal cancer: the European prospective investigation into cancer and nutrition study. Cancer Prev Res (Phila) 4:1873–1883. https://doi.org/10.1158/1940-6207.capr-11-0218

    Article  CAS  Google Scholar 

  34. Ahmed RL, Schmitz KH, Anderson KE, Rosamond WD, Folsom AR (2006) The metabolic syndrome and risk of incident colorectal cancer. Cancer 107:28–36. https://doi.org/10.1002/cncr.21950

    Article  PubMed  Google Scholar 

  35. Choi Y, Lee D, Han K, Shin C, Kim N (2018) Abdominal obesity, glucose intolerance and decreased high-density lipoprotein cholesterol as components of the metabolic syndrome are associated with the development of colorectal cancer. Eur J Epidemiol 33:1077–1085. https://doi.org/10.1007/s10654-018-0440-6

    Article  CAS  PubMed  Google Scholar 

  36. Lu Y, Ness-Jensen E, Hveem K, Martling A (2015) Metabolic predispositions and increased risk of colorectal adenocarcinoma by anatomical location: a large population-based cohort study in Norway. Am J Epidemiol 182:883–893. https://doi.org/10.1093/aje/kwv141

    Article  PubMed  Google Scholar 

  37. Stocks T, Lukanova A, Johansson M et al (2008) Components of the metabolic syndrome and colorectal cancer risk; a prospective study. Int J Obes (Lond) 32:304–314. https://doi.org/10.1038/sj.ijo.0803713

    Article  CAS  Google Scholar 

  38. Inoue M, Noda M, Kurahashi N et al (2009) Impact of metabolic factors on subsequent cancer risk: results from a large-scale population-based cohort study in Japan. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 18:240–247. https://doi.org/10.1097/CEJ.0b013e3283240460

    Article  Google Scholar 

  39. Shin HY, Jung KJ, Linton JA, Jee SH (2014) Association between fasting serum glucose levels and incidence of colorectal cancer in Korean men: the Korean Cancer Prevention Study-II. Metabolism 63:1250–1256. https://doi.org/10.1016/j.metabol.2014.07.006

    Article  CAS  PubMed  Google Scholar 

  40. de Ferranti S, Gauvreau K, Ludwig D et al (2004) Prevalence of the metabolic syndrome in American adolescents: findings from the Third National Health and Nutrition Examination Survey. Circulation 110:2494–2497. https://doi.org/10.1161/01.cir.0000145117.40114.c7

    Article  PubMed  Google Scholar 

  41. Ford E, Giles W, Dietz W (2002) Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287:356–359. https://doi.org/10.1001/jama.287.3.356

    Article  PubMed  Google Scholar 

  42. Sung H, Ferlay J, Siegel R et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. https://doi.org/10.3322/caac.21660

  43. Siegel R, Miller K, Jemal A (2020) Cancer statistics, 2020. CA Cancer J Clin 70:7–30. https://doi.org/10.3322/caac.21590

  44. Giovannucci E (2007) Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am J Clin Nutr 86:s836–s842. https://doi.org/10.1093/ajcn/86.3.836S

    Article  PubMed  Google Scholar 

  45. Komninou D, Ayonote A, Richie J, Rigas B (2003) Insulin resistance and its contribution to colon carcinogenesis. Exp Biol Med (Maywood) 228:396–405. https://doi.org/10.1177/153537020322800410

  46. Gallagher E, LeRoith D (2020) Hyperinsulinaemia in cancer. Nat Rev Cancer 20:629–644. https://doi.org/10.1038/s41568-020-0295-5

    Article  CAS  PubMed  Google Scholar 

  47. Godsland I (2009) Insulin resistance and hyperinsulinaemia in the development and progression of cancer. Clin Sci (Lond.) 118:315–32. https://doi.org/10.1042/cs20090399

  48. Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 8:915–928. https://doi.org/10.1038/nrc2536

    Article  CAS  PubMed  Google Scholar 

  49. Ma J, Pollak M, Giovannucci E et al (1999) Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 91:620–625. https://doi.org/10.1093/jnci/91.7.620

    Article  CAS  PubMed  Google Scholar 

  50. Harvey A, Lashinger L, Hursting S (2011) The growing challenge of obesity and cancer: an inflammatory issue. Ann N Y Acad Sci 1229:45–52. https://doi.org/10.1111/j.1749-6632.2011.06096.x

    Article  CAS  PubMed  Google Scholar 

  51. Quail D, Dannenberg A (2019) The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol 15:139–154. https://doi.org/10.1038/s41574-018-0126-x

    Article  PubMed  PubMed Central  Google Scholar 

  52. Fenton J, Hursting S, Perkins S, Hord N (2006) Interleukin-6 production induced by leptin treatment promotes cell proliferation in an Apc (Min/+) colon epithelial cell line. Carcinogenesis 27:1507–1515. https://doi.org/10.1093/carcin/bgl018

    Article  CAS  PubMed  Google Scholar 

  53. Karin M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441:431–436. https://doi.org/10.1038/nature04870

    Article  CAS  PubMed  Google Scholar 

  54. Sekeres M, Maciejewski J, List A et al (2011) Perceptions of disease state, treatment outcomes, and prognosis among patients with myelodysplastic syndromes: results from an internet-based survey. Oncologist 16:904–911. https://doi.org/10.1634/theoncologist.2010-0199

    Article  PubMed  PubMed Central  Google Scholar 

  55. Regitz-Zagrosek V, Lehmkuhl E, Mahmoodzadeh S (2007) Gender aspects of the role of the metabolic syndrome as a risk factor for cardiovascular disease. Gend Med S162–77. https://doi.org/10.1016/s1550-8579(07)80056-8

  56. Ng C, Jiang A, Toh E et al (2020) Metformin and colorectal cancer: a systematic review, meta-analysis and meta-regression. Int J Colorectal Dis 35:1501–1512. https://doi.org/10.1007/s00384-020-03676-x

    Article  PubMed  Google Scholar 

  57. Liu F, Yan L, Wang Z et al (2017) Metformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: a systematic review and meta-analysis. Oncotarget 8:16017–16026. https://doi.org/10.18632/oncotarget.13762

  58. Liu Y, Tang W, Wang J et al (2014) Association between statin use and colorectal cancer risk: a meta-analysis of 42 studies. Cancer causes & control : CCC 25:237–249. https://doi.org/10.1007/s10552-013-0326-6

    Article  CAS  PubMed  Google Scholar 

  59. Almazeedi S, El-Abd R, Al-Khamis A, Albatineh A, Al-Sabah S (2020) Role of bariatric surgery in reducing the risk of colorectal cancer: a meta-analysis. Br J Surg 107:348–354. https://doi.org/10.1002/bjs.11494

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by Sichuan Province Science and Technology Support Project (2018SZ0189).

Author information

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China

    Xiaoding Shen, Yong Wang, Rui Zhao, Qianyi Wan, Lihao Zhao & Xiaoting Wu

  2. West China School of Stomatology, Sichuan University, Chengdu, 610041, China

    Yutao Wu

Authors
  1. Xiaoding Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rui Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qianyi Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yutao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lihao Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaoting Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XDS, YW, and RZ contributed equally in this study. XDS and RZ searched relevant studies and contributed to the study selection. XDS and YW extracted data from included studies. All authors contributed to the data analysis and manuscript writing, and XTW approved the final manuscript.

Corresponding author

Correspondence to Xiaoting Wu.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Supplementary information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 530 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, X., Wang, Y., Zhao, R. et al. Metabolic syndrome and the risk of colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis 36, 2215–2225 (2021). https://doi.org/10.1007/s00384-021-03974-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-021-03974-y

Keywords

Search

Navigation