Epidemiology

Association of obesity status and metabolic syndrome with site-specific cancers: a population-based cohort study

Abstract

Background

Obesity and metabolic syndrome (MetS) appear in clusters and are both associated with an increased risk of cancer. However, it remains unknown whether obesity status with or without MetS increases the risk of site-specific cancers.

Methods

We used data derived from 390,575 individuals (37–73 years old) from the UK Biobank who were enrolled from 2006–2016 with a median of 7.8 years of follow-up. Obesity was defined by BMI ≥ 30 kg/m2 and MetS was defined by the criteria of the Adult Treatment Panel-III (ATP-III). Cox proportional hazards models were used to investigate the associations of BMI and MetS with 22 cancers.

Results

Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) phenotypes represented 6.7% and 17.9% of the total analytic samples and 27.1% and 72.9% of the included subpopulation with obesity, respectively. Obesity was independently associated with higher risks of 10 of 22 cancers. Stratified by metabolic status, the MUO phenotype was consistently associated with 10 obesity-related cancers. In contrast, the MHO phenotype was only associated with increased risks of five cancers: endometrium, oesophagus, kidney, pancreas and postmenopausal breast cancers.

Conclusion

Even in metabolically healthy individuals, obesity was associated with increased risks of five cancers, whereas we did not find that these individuals were associated with increased risks of several other obesity-related cancers.

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Fig. 1: Distribution of MetS criteria by metabolic health and obesity status.
Fig. 2: Incidence rate per 1000 person-year and multivariable HRs of cancers according to BMI categories.

References

  1. 1.

    NCD Risk Factor Collaboration. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 387, 1377–1396 (2016).

    Article  Google Scholar 

  2. 2.

    Choromanska, B., Mysliwiec, P., Razak Hady, H., Dadan, J., Mysliwiec, H., Chabowski, A. et al. Metabolic syndrome is associated with ceramide accumulation in visceral adipose tissue of women with morbid obesity. Obesity (Silver Spring) 27, 444–453 (2019).

    CAS  Google Scholar 

  3. 3.

    Choi, E. K., Park, H. B., Lee, K. H., Park, J. H., Eisenhut, M., van der Vliet, H. J. et al. Body mass index and 20 specific cancers: re-analyses of dose-response meta-analyses of observational studies. Ann. Oncol. 29, 749–757 (2018).

    CAS  Article  Google Scholar 

  4. 4.

    Saltiel, A. R. & Olefsky, J. M. Inflammatory mechanisms linking obesity and metabolic disease. J. Clin. Invest. 127, 1–4 (2017).

    Article  Google Scholar 

  5. 5.

    Kitahara, C. M., Pfeiffer, R. M., Sosa, J. A. & Shiels, M. S. Impact of overweight and obesity on U.S. papillary thyroid cancer incidence trends (1995–2015). J. Natl Cancer Inst. (2019). https://doi.org/10.1093/jnci/djz202.

  6. 6.

    Collaborators, G. R. F. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1923–1994 (2018).

    Article  Google Scholar 

  7. 7.

    Alberti, K. G., Eckel, R. H., Grundy, S. M., Zimmet, P. Z., Cleeman, J. I., Donato, K. A., et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 120, 1640–1645 (2009).

  8. 8.

    Karelis, A. D. Metabolically healthy but obese individuals. Lancet 372, 1281–1283 (2008).

    Article  Google Scholar 

  9. 9.

    Hinnouho, G. M., Czernichow, S., Dugravot, A., Batty, G. D., Kivimaki, M. & Singh-Manoux, A. Metabolically healthy obesity and risk of mortality: does the definition of metabolic health matter? Diabetes Care. 36, 2294–2300 (2013).

    CAS  Article  Google Scholar 

  10. 10.

    Hinnouho, G. M., Czernichow, S., Dugravot, A., Nabi, H., Brunner, E. J., Kivimaki, M. et al. Metabolically healthy obesity and the risk of cardiovascular disease and type 2 diabetes: the Whitehall II cohort study. Eur. Heart J. 36, 551–559 (2015).

    Article  Google Scholar 

  11. 11.

    Stefan, N., Haring, H. U., Hu, F. B. & Schulze, M. B. Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol. 1, 152–162 (2013).

    Article  Google Scholar 

  12. 12.

    Appleton, S. L., Seaborn, C. J., Visvanathan, R., Hill, C. L., Gill, T. K., Taylor, A. W. et al. Diabetes and cardiovascular disease outcomes in the metabolically healthy obese phenotype: a cohort study. Diabetes Care. 36, 2388–2394 (2013).

    Article  Google Scholar 

  13. 13.

    Murphy, N., Cross, A. J., Abubakar, M., Jenab, M., Aleksandrova, K., Boutron-Ruault, M. C. et al. A nested case-control study of metabolically defined body size phenotypes and risk of colorectal cancer in the European prospective investigation into cancer and nutrition (EPIC). PLoS Med. 13, e1001988 (2016).

    Article  Google Scholar 

  14. 14.

    Kabat, G. C., Kim, M. Y., Stefanick, M., Ho, G. Y. F., Lane, D. S., Odegaard, A. O. et al. Metabolic obesity phenotypes and risk of colorectal cancer in postmenopausal women. Int. J. Cancer 143, 543–551 (2018).

    CAS  Article  Google Scholar 

  15. 15.

    Park, Y. M., White, A. J., Nichols, H. B., O’Brien, K. M., Weinberg, C. R. & Sandler, D. P. The association between metabolic health, obesity phenotype and the risk of breast cancer. Int. J. Cancer 140, 2657–2666 (2017).

    CAS  Article  Google Scholar 

  16. 16.

    Moore, L. L., Chadid, S., Singer, M. R., Kreger, B. E. & Denis, G. V. Metabolic health reduces risk of obesity-related cancer in framingham study adults. Cancer Epidemiol. Biomark. Prev. 23, 2057–2065 (2014).

    CAS  Article  Google Scholar 

  17. 17.

    Dibaba, D. T., Ogunsina, K., Braithwaite, D. & Akinyemiju, T. Metabolic syndrome and risk of breast cancer mortality by menopause, obesity, and subtype. Cancers (Basel). 174, 209–218 (2019).

    CAS  Google Scholar 

  18. 18.

    Sung, H., Siegel, R. L., Torre, L. A., Pearson-Stuttard, J. & Islami, F. Global patterns in excess body weight and the associated cancer burden. CA Cancer J. Clin. 69, 88–112 (2019).

    PubMed  Google Scholar 

  19. 19.

    Bjorge, T., Haggstrom, C., Ghaderi, S., Nagel, G., Manjer, J., Tretli, S. et al. BMI and weight changes and risk of obesity-related cancers: a pooled European cohort study. Int. J. Epidemiol. 48, 1872–1885 (2019).

    Article  Google Scholar 

  20. 20.

    Sudlow, C., Gallacher, J., Allen, N., Beral, V., Burton, P., Danesh, J. et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12, e1001779 (2015).

    Article  Google Scholar 

  21. 21.

    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 (2001). https://doi.org/10.1001/jama.285.19.2486.

  22. 22.

    Martinez-Gomez, D., Ortega, F. B., Hamer, M., Lopez-Garcia, E., Struijk, E., Sadarangani, K. P. et al. Physical activity and risk of metabolic phenotypes of obesity: a prospective Taiwanese cohort study in more than 200,000 adults. Mayo Clin. Proc. 94, 2209–2219 (2019).

    Article  Google Scholar 

  23. 23.

    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) final report. Circulation 106, 3143–3421 (2002).

  24. 24.

    Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A. & Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018).

    Article  Google Scholar 

  25. 25.

    Lassale, C., Tzoulaki, I., Moons, K. G. M., Sweeting, M., Boer, J., Johnson, L. et al. Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis. Eur. Heart J. 39, 397–406 (2018).

    Article  Google Scholar 

  26. 26.

    Fang, X., Wei, J., He, X., Lian, J., Han, D., An, P. et al. Quantitative association between body mass index and the risk of cancer: a global Meta-analysis of prospective cohort studies. Int. J. Cancer 143, 1595–1603 (2018).

    CAS  Article  Google Scholar 

  27. 27.

    Yang, Y., Dong, J., Sun, K., Zhao, L., Zhao, F., Wang, L. et al. Obesity and incidence of lung cancer: a meta-analysis. Int. J. Cancer 132, 1162–1169 (2013).

    CAS  Article  Google Scholar 

  28. 28.

    Perez-Cornago, A., Key, T. J., Allen, N. E., Fensom, G. K., Bradbury, K. E., Martin, R. M. et al. Prospective investigation of risk factors for prostate cancer in the UK Biobank cohort study. Br. J. Cancer 117, 1562–1571 (2017).

    Article  Google Scholar 

  29. 29.

    Perez-Cornago, A., Appleby, P. N., Pischon, T., Tsilidis, K. K., Tjonneland, A., Olsen, A. et al. Tall height and obesity are associated with an increased risk of aggressive prostate cancer: results from the EPIC cohort study. BMC Med. 15, 115 (2017).

    Article  Google Scholar 

  30. 30.

    Bonn, S. E., Sjolander, A., Tillander, A., Wiklund, F., Gronberg, H. & Balter, K. Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk. Int. J. Cancer 139, 50–57 (2016).

    CAS  Article  Google Scholar 

  31. 31.

    Kwon, H., Chang, Y., Cho, A., Ahn, J., Park, S. E., Park, C. Y. et al. Metabolic obesity phenotypes and thyroid cancer risk: a cohort study. Thyroid 29, 349–358 (2019).

    Article  Google Scholar 

  32. 32.

    Lee, K. R., Seo, M. H., Do Han, K., Jung, J. & Hwang, I. C. Waist circumference and risk of 23 site-specific cancers: a population-based cohort study of Korean adults. Br. J. Cancer 119, 1018–1027 (2018).

    CAS  Article  Google Scholar 

  33. 33.

    Guo, W., Key, T. J. & Reeves, G. K. Adiposity and breast cancer risk in postmenopausal women: results from the UK Biobank prospective cohort. Int. J. Cancer 143, 1037–1046 (2018).

    CAS  Article  Google Scholar 

  34. 34.

    Lohmann, A. E., Goodwin, P. J., Chlebowski, R. T., Pan, K., Stambolic, V. & Dowling, R. J. Association of obesity-related metabolic disruptions with cancer risk and outcome. J. Clin. Oncol. 34, 4249–4255 (2016).

    Article  Google Scholar 

  35. 35.

    Janssen, I., Katzmarzyk, P. T. & Ross, R. Duration of overweight and metabolic health risk in American men and women. Ann. Epidemiol. 14, 585–591 (2004).

    Article  Google Scholar 

  36. 36.

    Aguilar-Salinas, C. A., Garcia, E. G., Robles, L., Riano, D., Ruiz-Gomez, D. G., Garcia-Ulloa, A. C. et al. High adiponectin concentrations are associated with the metabolically healthy obese phenotype. J. Clin. Endocrinol. Metab. 93, 4075–4079 (2008).

    CAS  Article  Google Scholar 

  37. 37.

    Ortega, F. B., Lee, D. C., Katzmarzyk, P. T., Ruiz, J. R., Sui, X., Church, T. S. et al. The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness. Eur. Heart J. 34, 389–397 (2013).

    Article  Google Scholar 

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Acknowledgements

We thank the participants of the UK Biobank. This research has been conducted using the UK Biobank Resource under the project number of 45676.

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Authors

Contributions

Z.C.: Conceptualisation, formal analysis, data curation, methodology, acquisition, software, writing—original draft. X.Z.: Conceptualisation, formal analysis, methodology, project software, writing—original draft. H.Y.: Formal analysis, data curation, methodology, acquisition, software and writing—review and editing. S.L.: Data curation, methodology, acquisition, software. F.X.: Data curation, methodology, software. X.Y.: Methodology, writing—review and editing. Y.W.: Conceptualisation, funding, project administration, acquisition and writing—review and editing.

Corresponding author

Correspondence to Yaogang Wang.

Ethics declarations

Ethics approval and consent to participate

UK Biobank has approval from the North West Multi-Centre Research Ethics Committee, the National Information Governance Board for Health & Social Care in England and Wales and the Community Health Index Advisory Group in Scotland. Written informed consent was provided by all participants. The study was performed in accordance with the Declaration of Helsinki.

Data availability

Information about data access is available online (http://www.ukbiobank.ac.uk/wp-content/uploads/2011/11/UK-Biobank-Protocol.pdf)

Competing interests

The authors declare no competing interests.

Funding information

This study was supported by the National Natural Science Foundation of China (grant No. 91746205, grants No. 71910107004 and grant No. 71673199).

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Cao, Z., Zheng, X., Yang, H. et al. Association of obesity status and metabolic syndrome with site-specific cancers: a population-based cohort study. Br J Cancer (2020). https://doi.org/10.1038/s41416-020-1012-6

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