Role of metabolic syndrome and lifestyle factors in endometrial cancer risk and prevention
DOI:
https://doi.org/10.12775/QS.2024.32.55862Keywords
endometrial caner, metabolic syndrome, lifestyle, prevention, risk factorsAbstract
Introduction: The incidence of endometrial cancer, the sixth most common cancer among women, has been rising, especially in developed countries, possibly due to the obesity and diabetes pandemic. The aim of this review is to investigate the connection between metabolic syndrome, its individual components and endometrial cancer risk and to explore the role of lifestyle factors in endometrial cancer prevention.
Materials and methods: For this review, we included studies regarding endometrial cancer and metabolic syndrome, obesity, diabetes and hyperglycemia, hypertension, dyslipidemia and several lifestyle factors, from 1994 to 2024.
State of knowledge: This paper reviews existing literature on the relationship between metabolic syndrome and endometrial cancer, highlighting the significant role of central obesity, hyperglycemia and diabetes, dyslipidemia, and hypertension as risk factors. Evidence consistently demonstrates that individuals with metabolic syndrome, and its components individually, are at a heightened risk of developing endometrial cancer compared to those without metabolic abnormalities. Biological mechanisms linking metabolic syndrome’s components to endometrial cancer involve complex interplays between metabolic, hormonal or inflammatory factors and signalling pathways. Lifestyle interventions focusing on weight management, physical activity, and eating habits play an important role in reducing endometrial cancer risk and improving overall health outcomes.
Conclusion: An understanding of the relationship between metabolic syndrome and endometrial cancer is crucial for improving risk stratification, early detection, and prevention strategies. Addressing metabolic abnormalities and promoting healthy lifestyle behaviours are essential actions against the rising incidence and burden of endometrial cancer.
References
Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. Published online April 4, 2024. doi:10.3322/caac.21834
Gu B, Shang X, Yan M, et al. Variations in incidence and mortality rates of endometrial cancer at the global, regional, and national levels, 1990–2019. Gynecol Oncol. 2021;161(2):573-580. doi:10.1016/j.ygyno.2021.01.036
Morice P, Leary A, Creutzberg C, Abu-Rustum N, Darai E. Endometrial cancer. In: The Lancet. Vol 387. Lancet Publishing Group; 2016:1094-1108. doi:10.1016/S0140-6736(15)00130-0
Paleari L, Pesce S, Rutigliani M, et al. New insights into endometrial cancer. Cancers (Basel). 2021;13(7). doi:10.3390/cancers13071496
Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I. Endometrial cancer. The Lancet. 2005;366(9484):491-505. doi:10.1016/S0140-6736(05)67063-8
Jones ER, O’Flynn H, Njoku K, Crosbie EJ. Detecting endometrial cancer. The Obstetrician & Gynaecologist. 2021;23(2):103-112. doi:10.1111/tog.12722
Lortet-Tieulent J, Ferlay J, Bray F, Jemal A. International patterns and trends in endometrial cancer incidence, 1978-2013. J Natl Cancer Inst. 2018;110(4):354-361. doi:10.1093/jnci/djx214
Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet. 2008;371(9612):569-578. doi:10.1016/S0140-6736(08)60269-X
Mili N, Paschou SA, Goulis DG, Dimopoulos MA, Lambrinoudaki I, Psaltopoulou T. Obesity, metabolic syndrome, and cancer: pathophysiological and therapeutic associations. Endocrine. 2021;74(3):478-497. doi:https://doi.org/10.1007/s12020-021-02884-x
Wang L, Du ZH, Qiao JM, Gao S. Association between metabolic syndrome and endometrial cancer risk: a systematic review and meta-analysis of observational studies. Aging. 2020;12(10):9825-9839. doi:10.18632/aging.103247
Huang PL. A comprehensive definition for metabolic syndrome. DMM Disease Models and Mechanisms. 2009;2(5-6):231-237. doi:10.1242/dmm.001180
Liao C, Zhang D, Mungo C, Andrew Tompkins D, Zeidan AM. Is diabetes mellitus associated with increased incidence and disease-specific mortality in endometrial cancer? A systematic review and meta-analysis of cohort studies. Gynecol Oncol. 2014;135(1):163-171. doi:10.1016/j.ygyno.2014.07.095
Zhang ZH, Su PY, Hao JH, Sun YH. The role of preexisting diabetes mellitus on incidence and mortality of endometrial cancer: A meta-analysis of prospective cohort studies. International Journal of Gynecological Cancer. 2013;23(2):294-303. doi:10.1097/IGC.0b013e31827b8430
Zabuliene L, Kaceniene A, Steponaviciene L, et al. Risk of endometrial cancer in women with diabetes: A population-based retrospective cohort study. J Clin Med. 2021;10(16). doi:10.3390/jcm10163453
Carstensen B, Read SH, Friis S, et al. Cancer incidence in persons with type 1 diabetes: a five-country study of 9,000 cancers in type 1 diabetic individuals. Diabetologia. 2016;59(5):980-988. doi:10.1007/s00125-016-3884-9
Pearson-Stuttard J, Papadimitriou N, Markozannes G, et al. Type 2 diabetes and cancer: An umbrella review of observational and mendelian randomization studies. Cancer Epidemiology Biomarkers and Prevention. 2021;30(6):1218-1228. doi:10.1158/1055-9965.EPI-20-1245
Byrne FL, Martin AR, Kosasih M, Caruana BT, Farrell R. The role of hyperglycemia in endometrial cancer pathogenesis. Cancers (Basel). 2020;12(5). doi:10.3390/cancers12051191
Saed L, Varse F, Baradaran HR, et al. The effect of diabetes on the risk of endometrial Cancer: An updated a systematic review and meta-analysis. BMC Cancer. 2019;19(1). doi:10.1186/s12885-019-5748-4
McVicker L, Cardwell CR, Edge L, et al. Survival outcomes in endometrial cancer patients according to diabetes: a systematic review and meta-analysis. BMC Cancer. 2022;22(1). doi:10.1186/s12885-022-09510-7
Luo J, Beresford S, Chen C, et al. Association between diabetes, diabetes treatment and risk of developing endometrial cancer. Br J Cancer. 2014;111(7):1432-1439. doi:10.1038/bjc.2014.407
Wang Y, Zeng X, Tan J, Xu Y, Yi C. Diabetes mellitus and endometrial carcinoma: Risk factors and etiological links. Medicine (United States). 2022;101(34):E30299. doi:10.1097/MD.0000000000030299
Friberg E, Orsini N, Mantzoros CS, Wolk A. Diabetes mellitus and risk of endometrial cancer: A meta-analysis. Diabetologia. 2007;50(7):1365-1374. doi:10.1007/s00125-007-0681-5
Han J, Zhang L, Guo H, et al. Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling. Gynecol Oncol. 2015;138(3):668-675. doi:10.1016/j.ygyno.2015.06.036
Zhang Y, Liu H, Yang S, Zhang J, Qian L, Chen X. Overweight, obesity and endometrial cancer risk: Results from a systematic review and meta-analysis. International Journal of Biological Markers. 2014;29(1). doi:10.5301/jbm.5000047
Jenabi E, Poorolajal J. The effect of body mass index on endometrial cancer: A meta-analysis. Public Health. 2015;129(7):872-880. doi:10.1016/j.puhe.2015.04.017
Harvey S V., Wentzensen N, Bertrand K, et al. Associations of life course obesity with endometrial cancer in the Epidemiology of Endometrial Cancer Consortium (E2C2). Int J Epidemiol. 2023;52(4):1086-1099. doi:10.1093/ije/dyad046
Crosbie EJ, Zwahlen M, Kitchener HC, Egger M, Renehan AG. Body mass index, hormone replacement therapy, and endometrial cancer risk: A meta-analysis. Cancer Epidemiology Biomarkers and Prevention. 2010;19(12):3119-3130. doi:10.1158/1055-9965.EPI-10-0832
Aune D, Navarro Rosenblatt DA, Chan DSM, et al. Anthropometric factors and endometrial cancer risk: A systematic review and dose-response meta-analysis of prospective studies. Annals of Oncology. 2015;26(8):1635-1648. doi:10.1093/annonc/mdv142
Secord AA, Hasselblad V, Von Gruenigen VE, et al. Body mass index and mortality in endometrial cancer: A systematic review and meta-analysis. Gynecol Oncol. 2016;140(1):184-190. doi:10.1016/j.ygyno.2015.10.020
Kokts‐Porietis RL, Elmrayed S, Brenner DR, Friedenreich CM. Obesity and mortality among endometrial cancer survivors: A systematic review and meta‐analysis. Obesity Reviews. 2021;22(12). doi:10.1111/obr.13337
SIMPSON ER, MAHENDROO MS, MEANS GD, et al. Aromatase Cytochrome P450, The Enzyme Responsible for Estrogen Biosynthesis*. Endocr Rev. 1994;15(3):342-355. doi:10.1210/edrv-15-3-342
Meinhardt U, Mullis PE. The Aromatase Cytochrome P-450 and Its Clinical Impact. Horm Res Paediatr. 2002;57(5-6):145-152. doi:10.1159/000058374
Kitson SJ, Crosbie EJ. Endometrial cancer and obesity. The Obstetrician & Gynaecologist. 2019;21(4):237-245. doi:10.1111/tog.12601
Kiesel L, Eichbaum C, Baumeier A, Eichbaum M. Obesity epidemic—the underestimated risk of endometrial cancer. Cancers (Basel). 2020;12(12):1-11. doi:10.3390/cancers12123860
Lee CH, Woo YC, Wang Y, Yeung CY, Xu A, Lam KSL. Obesity, adipokines and cancer: An update. Clin Endocrinol (Oxf). 2015;83(2):147-156. doi:10.1111/cen.12667
Ellis PE, Barron GA, Bermano G. Adipocytokines and their relationship to endometrial cancer risk: A systematic review and meta-analysis. Gynecol Oncol. 2020;158(2):507-516. doi:10.1016/j.ygyno.2020.05.033
Stępień S, Olczyk P, Gola J, Komosińska-Vassev K, Mielczarek-Palacz A. The Role of Selected Adipocytokines in Ovarian Cancer and Endometrial Cancer. Cells. 2023;12(8). doi:10.3390/cells12081118
Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. Journal of Clinical Investigation. 2006;116(7):1784-1792. doi:10.1172/JCI29126
Soliman PT, Wu D, Tortolero-Luna G, et al. Association between adiponectin, insulin resistance, and endometrial cancer. Cancer. 2006;106(11):2376-2381. doi:10.1002/cncr.21866
Dal Maso L, Augustin LSA, Karalis A, et al. Circulating adiponectin and endometrial cancer risk. Journal of Clinical Endocrinology and Metabolism. 2004;89(3):1160-1163. doi:10.1210/jc.2003-031716
Zheng Q, Wu H, Cao J. Circulating adiponectin and risk of endometrial cancer. PLoS One. 2015;10(6). doi:10.1371/journal.pone.0129824
Habeshian TS, Peeri NC, De Vivo I, et al. Hypertension and Risk of Endometrial Cancer: A Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2). Cancer Epidemiology, Biomarkers & Prevention. Published online April 11, 2024:OF1-OF8. doi:10.1158/1055-9965.EPI-23-1444
Weiderpass E, Persson I, Adami HO, Magnusson C, Lindgren A, Baron JA. Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer (Sweden). Cancer Causes and Control. 2000;11(2):185-192. doi:10.1023/A:1008946825313
Aune D, Sen A, Vatten LJ. Hypertension and the risk of endometrial cancer: A systematic review and meta-analysis of case-control and cohort studies. Sci Rep. 2017;7. doi:10.1038/srep44808
Nicholas Z, Hu N, Ying J, Soisson P, Dodson M, Gaffney DK. Impact of comorbid conditions on survival in endometrial cancer. American Journal of Clinical Oncology: Cancer Clinical Trials. 2014;37(2):131-134. doi:10.1097/COC.0b013e318277d5f4
Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Giugliano D. Metabolic syndrome and endometrial cancer: A meta-analysis. Endocrine. 2014;45(1):28-36. doi:10.1007/s12020-013-9973-3
Seth D, Garmo H, Wigertz A, et al. Lipid profiles and the risk of endometrial cancer in the Swedish AMORIS study. Int J Mol Epidemiol Genet. 2012;3(2):122-133.
Dossus L, Lukanova A, Rinaldi S, et al. Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort - A factor analysis. Am J Epidemiol. 2013;177(8):787-799. doi:10.1093/aje/kws309
Lindemann K, Vatten LJ, Ellstrøm-Engh M, Eskild A. Serum lipids and endometrial cancer risk: Results from the HUNT-II study. Int J Cancer. 2009;124(12):2938-2941. doi:10.1002/ijc.24285
Zhang X, Rhoades J, Caan BJ, et al. Intentional weight loss, weight cycling, and endometrial cancer risk: A systematic review and meta-analysis. International Journal of Gynecological Cancer. 2019;29(9):1361-1371. doi:10.1136/ijgc-2019-000728
Naqvi A, MacKintosh ML, Derbyshire AE, et al. The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium. Int J Obes. 2022;46(3):605-612. doi:10.1038/s41366-021-01027-6
Raskov H, Orhan A, Christensen JP, Gögenur I. Cytotoxic CD8+ T cells in cancer and cancer immunotherapy. Br J Cancer. 2021;124(2):359-367. doi:10.1038/s41416-020-01048-4
Esposito G, Bravi F, Serraino D, et al. Diabetes risk reduction diet and endometrial cancer risk. Nutrients. 2021;13(8). doi:10.3390/nu13082630
Filomeno M, Bosetti C, Bidoli E, et al. Mediterranean diet and risk of endometrial cancer: A pooled analysis of three italian case-control studies. Br J Cancer. 2015;112(11):1816-1821. doi:10.1038/bjc.2015.153
Lu YT, Gunathilake M, Kim J. The influence of dietary vegetables and fruits on endometrial cancer risk: a meta-analysis of observational studies. Eur J Clin Nutr. 2023;77(5):561-573. doi:10.1038/s41430-022-01213-3
Nagle CM, Olsen CM, Ibiebele TI, Spurdle AB, Webb PM. Glycemic index, glycemic load and endometrial cancer risk: results from the Australian National Endometrial Cancer study and an updated systematic review and meta-analysis. Eur J Nutr. 2013;52(2):705-715. doi:10.1007/s00394-012-0376-7
Cantrell LA, Zhou C, Mendivil A, Malloy KM, Gehrig PA, Bae-Jump VL. Metformin is a potent inhibitor of endometrial cancer cell proliferation—implications for a novel treatment strategy. Gynecol Oncol. 2010;116(1):92-98. doi:10.1016/j.ygyno.2009.09.024
Zhao Y, Sun H, Feng M, et al. Metformin is associated with reduced cell proliferation in human endometrial cancer by inbibiting PI3K/AKT/mTOR signaling. Gynecological Endocrinology. 2018;34(5):428-432. doi:10.1080/09513590.2017.1409714
Chu D, Wu J, Wang K, et al. Effect of metformin use on the risk and prognosis of endometrial cancer: A systematic review and meta-analysis. BMC Cancer. 2018;18(1). doi:10.1186/s12885-018-4334-5
Kitson SJ, Aurangzeb O, Parvaiz J, Lophatananon A, Muir KR, Crosbie EJ. Quantifying the Effect of Physical Activity on Endometrial Cancer Risk. Cancer Prevention Research. 2022;15(9):605-621. doi:10.1158/1940-6207.CAPR-22-0129
Mctiernan A, Tworoger SS, Ulrich CM, et al. Effect of Exercise on Serum Estrogens in Postmenopausal Women: A 12-Month Randomized Clinical Trial. Vol 64.; 2004. http://aacrjournals.org/cancerres/article-pdf/64/8/2923/2529002/zch00804002923.pdf
Schmid D, Behrens G, Keimling M, Jochem C, Ricci C, Leitzmann M. A systematic review and meta-analysis of physical activity and endometrial cancer risk. Eur J Epidemiol. 2015;30(5):397-412. doi:10.1007/s10654-015-0017-6
Moore SC, Gierach GL, Schatzkin A, Matthews CE. Physical activity, sedentary behaviours, and the prevention of endometrial cancer. Br J Cancer. 2010;103(7):933-938. doi:10.1038/sj.bjc.6605902
Esposito G, Turati F, Serraino D, et al. Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations and endometrial cancer risk: A multicentric case-control study. British Journal of Nutrition. 2023;129(12):2133-2141. doi:10.1017/S0007114522002872
Connor E V., Raker CA, Clark MA, Stuckey AR. Obesity risk awareness in women with endometrial cancer. Arch Gynecol Obstet. 2017;295(4):965-969. doi:10.1007/s00404-017-4301-4
Washington CR, Haggerty A, Ronner W, Neff PM, Ko EM. Knowledge of endometrial cancer risk factors in a general gynecologic population. Gynecol Oncol. 2020;158(1):137-142. doi:10.1016/j.ygyno.2020.03.032
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Anita Kwiatkowska, Natalia Małek, Sara Emerla, Aleksandra Brożyna, Arkadiusz Bydliński, Konrad Karłowicz, Maria Hermanowska, Julia Lubomirska, Patrycja Figurowska, Łukasz Ciulkiewicz
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 122
Number of citations: 0