Impact of obesity on the development of malignant tumors – metabolic syndrome
Authors:
L. Gescheidtová 1,2; Z. Čermáková 1,2
Authors‘ workplace:
Oddělení laboratorní medicíny, MOÚ, Brno2 Oddělení specializovaných ambulancí, MOÚ, Brno
1
Published in:
Klin Onkol 2026; 39(Supplementum 1): 36-40
Category:
Review
doi:
https://doi.org/10.48095/ccko2026S36
Overview
Background: Obesity is a major and modifiable risk factor influencing both the incidence and prognosis of malignant tumors. Aim: This review aims to summarize current evidence on the relationship between obesity, metabolic syndrome, and cancer risk, with a focus on underlying pathophysiological mechanisms, epidemiological data, and potential interventions. According to the International Agency for Research on Cancer, obesity is causally linked to at least 13 types of cancer, with risk increasing in proportion to body fat. Key mechanisms include chronic inflammation, hormonal activity of adipose tissue, hyperinsulinemia and insulin resistance, and alterations in adipokine profiles, all of which contribute to a tumor-promoting microenvironment. We discuss diagnostic criteria for metabolic syndrome and highlight the concept of metabolically healthy obesity, which carries a lower – but not negligible – risk of malignancy and represents a dynamic state that can progress to metabolically unhealthy obesity. Evidence also indicates that obesity negatively affects cancer recurrence and long-term outcomes, particularly in breast, endometrial, and colorectal cancers. Achieving sustainable, long-term weight reduction is challenging and requires a multidisciplinary strategy, incorporating pharmacotherapy, structured physical activity, behavioral interventions, and individualized nutritional counseling. Successful weight loss not only reduces the risk of developing cancer but may also improve prognosis and decrease the likelihood of recurrence. Therefore, integrating obesity management strategies into both primary and secondary cancer prevention, as well as survivorship care, should be considered a critical component of comprehensive oncology care.
Keywords:
obesity – metabolic syndrome – cancer risk
Sources
1. World Cancer Research Fund. Diet, nutrition, physical activity and cancer: a global perspective. A summary of the third expert report. [online]. Available from: https: //www.wcrf.org/wp-content/uploads/2024/11/Summary-of-Third-Expert-Report-2018.pdf.
2. Green J, Reeves GK, Floud S et al. Cohort profile: the million women study. Int J Epidemiol 2019; 48 (1): 28–29. doi: 10.1093/ije/dyy065.
3. Lauby-Secretan B, Scoccianti C, Loomis D et al. Body fatness and cancer – viewpoint of the IARC working group. N Engl J Med 2016; 375 (8): 794–798. doi: 10.1056/NEJMsr1606602.
4. Landovská P, Karbanová M. Social costs of obesity in the Czech Republic. Eur J Health Econ 2023; 24 (8): 1321–1341. doi: 10.1007/s10198-022-01545-8.
5. Statbase. Prevalence of obesity among adults | Czech Republic. [online]. Available from: https: //statbase.org/data/cze-prevalence-of-obesity-among-adults/.
6. World Health Organisation. The challenge of obesity. [online]. Available from: https: //www.who.int/europe/news-room/fact-sheets/item/the-challenge-of-obesity.
7. Vesikansa A, Mehtälä J, Aspholm S et al. Indirect costs constitute a major part of the total economic burden of obesity: a Finnish population-based cohort study. BMC Public Health 2025; 25 (1): 1739. doi: 10.1186/s12889-025-22978-9.
8. Alberti KG, Eckel RH, Grundy SM 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 2009; 120 (16): 1640–1645. doi: 10.1161/CIRCULATIONAHA.109.192644.
9. Lin H, Zhang L, Zheng R et al. The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: a systematic review and meta-analysis: a PRISMA-compliant article. Medicine (Baltimore) 2017; 96 (47): e8838. doi: 10.1097/MD.0000000000008838.
10. Shin S, Kim JM, Sung S et al. Prevalence and associated characteristics of metabolically healthy obese phenotypes in a community dwelling population. J Obes Metab Syndr 2017; 26 (2): 130–137. doi: 10.7570/jomes.2017.26.2.130.
11. van Vliet-Ostaptchouk JV, Nuotio ML, Slagter SN et al. The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies. BMC Endocr Disord 2014; 14 : 9. doi: 10.1186/1472-6823-14-9.
12. Eckel N, Meidtner K, Kalle-Uhlmann T et al. Metabolically healthy obesity and cardiovascular events: a systematic review and meta-analysis. Eur J Prev Cardiol 2016; 23 (9): 956–966. doi: 10.1177/2047487315623884.
13. Lin CJ, Chang YC, Cheng TY et al. The association between metabolically healthy obesity and risk of cancer: a systematic review and meta-analysis of prospective cohort studies. Obes Rev 2020; 21 (10): e13049. doi: 10.1111/obr.13049.
14. Wang H, Li J, Liu S et al. Metabolic obesity phenotypes and their transitions as determinants of multimorbidity trajectories: evidence from global aging cohorts. Diabetol Metab Syndr 2025; 17 (1): 447. doi: 10.1186/s13098-025-01992-2.
15. Netto AM, Kashiwagi NM, Minanni CA et al. Adiposity, hepatic steatosis, and metabolic health transitions in people with obesity: influences of age and sex. Nutr Metab Cardiovasc Dis 2023; 33 (6): 1149–1157. doi: 10.1016/j.numecd.2023.03.020.
16. Clontz AD, Gan E, Hursting SD et al. Effects of weight loss on key obesity-related biomarkers linked to the risk of endometrial cancer: a systematic review and meta-analysis. Cancers (Basel) 2024; 16 (12). doi: 10.3390/cancers16122197.
17. Aleksandrova K, Nimptsch K, Pischon T. Influence of obesity and related metabolic alterations on colorectal cancer risk. Curr Nutr Rep 2013; 2 (1): 1–9. doi: 10.1007/s13668-012-0036-9.
18. Ungvari Z, Fekete M, Varga P et al. Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25–57% elevation in risk. Geroscience 2025; 47 (3): 3343–3364. doi: 10.1007/s11357-024-01375-x.
19. Zhang W, An Y, Qin X et al. Gut microbiota-derived metabolites in colorectal cancer: the bad and the challenges. Front Oncol 2021; 11 : 739648. doi: 10.3389/fonc.2021.739648.
20. Ocvirk S, O‘Keefe SJ. Influence of bile acids on colorectal cancer risk: potential mechanisms mediated by diet – gut microbiota interactions. Curr Nutr Rep 2017; 6 (4): 315–322. doi: 10.1007/s13668-017-0219-5.
21. Karahalios A, English DR, Simpson JA. Weight change and risk of colorectal cancer: a systematic review and meta-analysis. Am J Epidemiol 2015; 181 (11): 832–845. doi: 10.1093/aje/kwu357.
22. Fontvieille E, Viallon V, Recalde M et al. Body mass index and cancer risk among adults with and without cardiometabolic diseases: evidence from the EPIC and UK biobank prospective cohort studies. BMC Med 2023; 21 (1): 418. doi: 10.1186/s12916-023-03114-z.
23. Renehan AG, Tyson M, Egger M et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371 (9612): 569–578. doi: 10.1016/S0140-6736 (08) 60269-X.
24. Harrison S, Tilling K, Turner EL et al. Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen. Cancer Causes Control 2020; 31 (5): 431–449. doi: 10.1007/s10552-020-01291-3.
25. Mahamat-Saleh Y, Aune D, Freisling H et al. Association of metabolic obesity phenotypes with risk of overall and site-specific cancers: a systematic review and meta-analysis of cohort studies. Br J Cancer 2024; 131 (9): 1480–1495. doi: 10.1038/s41416-024-02857-7.
26. Li S, Chen L, Jin W et al. Influence of body mass index on incidence and prognosis of acute myeloid leukemia and acute promyelocytic leukemia: a meta-analysis. Sci Rep 2017; 7 (1): 17998. doi: 10.1038/s41598-017-18278-x.
27. Larsson SC, Wolk A. Obesity and risk of non-Hodgkin lymphoma: a meta-analysis. Int J Cancer 2007; 121 (7): 1564–1570. doi: 10.1002/ijc.22762.
28. Whitlock G, Lewington S, Sherliker P et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 2009; 373 (9669): 1083–1096. doi: 10.1016/S0140-6736 (09) 60318-4.
29. Eliassen AH, Colditz GA, Rosner B et al. Adult weight change and risk of postmenopausal breast cancer. JAMA 2006; 296 (2): 193–201. doi: 10.1001/jama.296.2.193.
30. Petrelli F, Cortellini A, Indini A et al. Association of obesity with survival outcomes in patients with cancer: a systematic review and meta-analysis. JAMA Netw Open 2021; 4 (3): e213520. doi: 10.1001/jamanetworkopen.2021.3520.
31. Chan DSM, Vieira AR, Aune D et al. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol 2014; 25 (10): 1901–1914. doi: 10.1093/annonc/mdu042.
32. Protani M, Coory M, Martin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 2010; 123 (3): 627–635. doi: 10.1007/s10549-010-0990-0.
33. Doleman B, Mills KT, Lim S et al. Body mass index and colorectal cancer prognosis: a systematic review and meta-analysis. Tech Coloproctol 2016; 20 (8): 517–535. doi: 10.1007/s10151-016-1498-3.
34. Sinicrope FA, Foster NR, Sargent DJ et al. Obesity is an independent prognostic variable in colon cancer survivors. Clin Cancer Res 2010; 16 (6): 1884–1893. doi: 10.1158/1078-0432.CCR-09-2636.
35. Courneya KS, Vardy JL, O‘Callaghan CJ et al. Structured exercise after adjuvant chemotherapy for colon cancer. N Engl J Med 2025; 393 (1): 13–25. doi: 10.1056/NEJMoa2502760.
36. Cao Y, Ma J. Body mass index, prostate cancer-specific mortality, and biochemical recurrence: a systematic review and meta-analysis. Cancer Prev Res (Phila) 2011; 4 (4): 486–501. doi: 10.1158/1940-6207.CAPR-10-0229.
37. Crosbie EJ, Zwahlen M, Kitchener HC et al. Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2010; 19 (12): 3119–3130. doi: 10.1158/1055-9965.EPI-10-0832.
38. Protani MM, Nagle CM, Webb PM. Obesity and ovarian cancer survival: a systematic review and meta-analysis. Cancer Prev Res (Phila) 2012; 5 (7): 901–910. doi: 10.1158/1940-6207.CAPR-12-0048.
39. Gluba-Brzózka A, Rysz J, Ławiński J et al. Renal cell cancer and obesity. Int J Mol Sci 2022; 23 (6). doi: 10.3390/ijms23063404.
40. Ligibel JA, Alfano CM, Courneya KS et al. American society of clinical oncology position statement on obesity and cancer. J Clin Oncol 2014; 32 (31): 3568–3574. doi: 10.1200/JCO.2014.58.4680.
41. Darby SC, Ewertz M, McGale P et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 2013; 368 (11): 987–998. doi: 10.1056/NEJMoa1209825.
42. Kaboré EG, Guenancia C, Vaz-Luis I et al. Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study. PLoS Med 2019; 16 (12): e1002989. doi: 10.1371/journal.pmed.1002989.
43. Sjöström L, Gummesson A, Sjöström CD et al. Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish obese subjects study): a prospective, controlled intervention trial. Lancet Oncol 2009; 10 (7): 653–662. doi: 10.1016/S1470-2045 (09) 70159-7.
44. Schauer DP, Feigelson HS, Koebnick C et al. Bariatric surgery and the risk of cancer in a large multisite cohort. Ann Surg 2019; 269 (1): 95–101. doi: 10.1097/SLA.0000000000002525.
45. Fearon K, Strasser F, Anker SD et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 12 (5): 489–495. doi: 10.1016/S1470-2045 (10) 70218-7.
46. LeBlanc ES, Patnode CD, Webber EM et al. Behavioral and pharmacotherapy weight loss interventions to prevent obesity-related morbidity and mortality in adults: updated evidence report and systematic review for the US preventive services task force. JAMA 2018; 320 (11): 1172–1191. doi: 10.1001/jama.2018.7777.
47. F Piepoli M. 2016 European guidelines on cardiovascular disease prevention in clinical practice. Int J Behav Med 2017; 24 (3): 321–419. doi: 10.1007/s12529-016-9583-6.
48. Yeh HC, Bantle JP, Cassidy-Begay M et al. Intensive weight loss intervention and cancer risk in adults with type 2 diabetes: analysis of the look AHEAD randomized clinical trial. Obesity (Silver Spring) 2020; 28 (9): 1678–1686. doi: 10.1002/oby.22936.
49. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006; 444 (7121): 860–867. doi: 10.1038/nature05485.
50. Weisberg SP, McCann D, Desai M et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112 (12): 1796–1808. doi: 10.1172/JCI19246.
51. Xu H, Barnes GT, Yang Q et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112 (12): 1821–1830. doi: 10.1172/JCI19451.
52. Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes (Lond) 2009; 33 (1): 54–66. doi: 10.1038/ijo.2008.229.
53. Furukawa S, Fujita T, Shimabukuro M et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004; 114 (12): 1752–1761. doi: 10.1172/JCI21625.
54. Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology 2007; 132 (6): 2169–2180. doi: 10.1053/j.gastro.2007.03.059.
55. Garofalo C, Surmacz E. Leptin and cancer. J Cell Physiol 2006; 207 (1): 12–22. doi: 10.1002/jcp.20472.
56. Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocr Rev 2012; 33 (4): 547–594. doi: 10.1210/er.2011-1015.
57. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89 (6): 2548–2556. doi: 10.1210/jc.2004-0395.
58. Simpson ER, Misso M, Hewitt KN et al. Estrogen – the good, the bad, and the unexpected. Endocr Rev 2005; 26 (3): 322–330. doi: 10.1210/er.2004-0020.
59. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004; 4 (8): 579–591. doi: 10.1038/nrc1408.
60. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 2008; 8 (12): 915–928. doi: 10.1038/nrc2536.
61. Giovannucci E. Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 2001; 131 (11 Suppl): 3109S–3120S. doi: 10.1093/jn/131.11.3109S.
62. Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 2000; 92 (18): 1472–1489. doi: 10.1093/jnci/92.18.1472.
63. Iyengar NM, Gucalp A, Dannenberg AJ et al. Obesity and cancer mechanisms: tumor microenvironment and inflammation. J Clin Oncol 2016; 34 (35): 4270–4276. doi: 10.1200/JCO.2016.67.4283.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2026 Issue Supplementum 1
-
All articles in this issue
- Editorial
- Cancer screening programmes in the Czech Republic and their results
- Polygenic risk score and its role in cancer susceptibility
- Multicancer early detection (MCED) tests – an overview of technologies and clinical evidence
- Physical activity in cancer prevention
- Nicotine products on the market and cancer risk
- Impact of obesity on the development of malignant tumors – metabolic syndrome
- Mental health and sleep in cancer prevention – removing barriers to health
- Environmental exposure and cancer prevention in the Czech Republic
- OncoVis: carcinogenic substances, their classification and potential impact on cancer development – an interactive dashboard for clinical practice
- Disruption of hormonal balance and the potential development of cancer – the impact of endocrine disruptors
- Microplastic in human body – a critical insight into current microplastic research
- Microbiome in early cancer detection – biomarker potential and limitations
- Probiotics, postbiotics, and synbiotics in the prevention of oncological diseases
- Clinical Oncology
- Journal archive
- Current issue
- Online only
- About the journal
Most read in this issue
- Multicancer early detection (MCED) tests – an overview of technologies and clinical evidence
- OncoVis: carcinogenic substances, their classification and potential impact on cancer development – an interactive dashboard for clinical practice
- Cancer screening programmes in the Czech Republic and their results
- Editorial