Release Date: 2023-09-14

Diabetes Mellitus: Effects on Cancer Risk Overview

Afife Uguz (Author)

Release Date: 2023-09-14

Diabetes mellitus (DM) has been increasingly recognized for its association with cancer risk and outcomes. Individuals with diabetes are at a higher risk of developing certain types of cancer compared to the general population. The relationship between DM and cancer is multifactorial, involving shared risk factors such as obesity, sedentary lifestyle, and dietary habits. Mechanisms [...]

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Work TypeBook Chapter
Published inCurrent Perspective on Diabetes Mellitus in Clinical Sciences
First Page489
Last Page502
DOIhttps://doi.org/10.69860/nobel.9786053359111.44
ISBN978-605-335-911-1 (PDF)
LanguageENG
Page Count14
Copyright HolderNobel Tıp Kitabevleri
Licensehttps://nobelpub.com/publish-with-us/copyright-and-licensing

Diabetes mellitus (DM) has been increasingly recognized for its association with cancer risk and outcomes. Individuals with diabetes are at a higher risk of developing certain types of cancer compared to the general population. The relationship between DM and cancer is multifactorial, involving shared risk factors such as obesity, sedentary lifestyle, and dietary habits. Mechanisms underlying this association include hyperinsulinemia, insulin resistance, chronic inflammation, and alterations in growth factors like insulin-like growth factor (IGF) and adipokines. These metabolic disturbances can promote carcinogenesis by facilitating cell proliferation, inhibiting apoptosis, and enhancing angiogenesis. Moreover, diabetes management, including medications like metformin, has been studied for its potential protective effects against certain cancers. However, the impact of diabetes on cancer outcomes remains complex, influencing prognosis and treatment responses. Integrated approaches addressing both diabetes control and cancer screening are crucial in clinical practice to mitigate the dual burden of these chronic conditions and improve overall patient outcomes.

Afife Uguz (Author)
MD, Karaman Training and Research Hospital
https://orcid.org/0000-0002-3886-5099

  • Greenwood M, Wood F. The Relation between the Cancer and Diabetes Death-rates. The Journal of hygiene. 1914;14(1):83-118.

  • Suh S, Kim KW. Diabetes and Cancer: Cancer Should Be Screened in Routine Diabetes Assessment. Diabetes & metabolism journal. 2019;43(6):733-43.

  • Shahid RK, Ahmed S, Le D, Yadav S. Diabetes and Cancer: Risk, Challenges, Management and Outcomes. Cancers. 2021;13(22).

  • Skyler JS, Bakris GL, Bonifacio E, Darsow T, Eckel RH, Groop L, et al. Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis. Diabetes. 2017;66(2):241-55.

  • Cignarelli A, Genchi VA, Caruso I, Natalicchio A, Perrini S, Laviola L, et al. Diabetes and cancer: Pathophysiological fundamentals of a ‘dangerous affair’. Diabetes research and clinical practice. 2018;143:378- 88.

  • Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: a consensus report. Diabetes care. 2010;33(7):1674-85.

  • Kirkman MS, Briscoe VJ, Clark N, Florez H, Haas LB, Halter JB, et al. Diabetes in older adults. Diabetes care. 2012;35(12):2650-64.

  • Carstensen B, Read SH, Friis S, Sund R, Keskimäki I, Svensson AM, et al. Cancer incidence in persons with type 1 diabetes: a fi ve-country study of 9,000 cancers in type 1 diabetic individuals. Diabetologia. 2016;59(5):980-8.

  • Lega IC, Lipscombe LL. Review: Diabetes, Obesity, and Cancer-Pathophysiology and Clinical Implications. Endocrine reviews. 2020;41(1).

  • Shu X, Ji J, Li X, Sundquist J, Sundquist K, Hemminki K. Cancer risk among patients hospitalized for Type 1 diabetes mellitus: a population-based cohort study in Sweden. Diabetic medicine : a journal of the British Diabetic Association. 2010;27(7):791-7.

  • Sona MF, Myung SK, Park K, Jargalsaikhan G. Type 1 diabetes mellitus and risk of cancer: a meta-analysis of observational studies. Japanese journal of clinical oncology. 2018;48(5):426-33.

  • Stevens RJ, Roddam AW, Beral V. Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta-analysis. British journal of cancer. 2007;96(3):507-9

  • Harding JL, Shaw JE, Peeters A, Cartensen B, Magliano DJ. Cancer risk among people with type 1 and type 2 diabetes: disentangling true associations, detection bias, and reverse causation. Diabetes care. 2015;38(2):264-70.

  • Kasper JS, Giovannucci E. A meta-analysis of diabetes mellitus and the risk of prostate cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2006;15(11):2056-62.

  • Tsilidis KK, Kasimis JC, Lopez DS, Ntzani EE, Ioannidis JP. Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ (Clinical research ed). 2015;350:g7607.

  • Atchison EA, Gridley G, Carreon JD, Leitzmann MF, McGlynn KA. Risk of cancer in a large cohort of U.S. veterans with diabetes. International journal of cancer. 2011;128(3):635-43.

  • Li H, Qian J. Association of diabetes mellitus with thyroid cancer risk: A meta-analysis of cohort studies. Medicine. 2017;96(47):e8230.

  • Ramos-Garcia P, Roca-Rodriguez MDM, Aguilar-Diosdado M, Gonzalez-Moles MA. Diabetes mellitus and oral cancer/oral potentially malignant disorders: A systematic review and meta-analysis. Oral diseases. 2021;27(3):404-21.

  • Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocrine-related cancer. 2009;16(4):1103-23.

  • Zhao L, Zheng Z, Huang P. Diabetes mellitus and the risk of glioma: a meta-analysis. Oncotarget. 2016;7(4):4483-9.

  • Jian Gang P, Mo L, Lu Y, Runqi L, Xing Z. Diabetes mellitus and the risk of prostate cancer: an update and cumulative meta-analysis. Endocrine research. 2015;40(1):54-61.

  • Ariaans G, de Jong S, Gietema JA, Lefrandt JD, de Vries EG, Jalving M. Cancer-drug induced insulin resistance: innocent bystander or unusual suspect. Cancer treatment reviews. 2015;41(4):376-84.

  • Gallo M, Muscogiuri G, Felicetti F, Faggiano A, Trimarchi F, Arvat E, et al. Adverse glycaemic effects of cancer therapy: indications for a rational approach to cancer patients with diabetes. Metabolism: clinical and experimental. 2018;78:141-54.

  • 2. Classifi cation and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2021. Diabetes care. 2021;44(Suppl 1):S15-s33.

  • Ewald N, Kaufmann C, Raspe A, Kloer HU, Bretzel RG, Hardt PD. Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c). Diabetes/metabolism research and reviews. 2012;28(4):338-42.

  • Hart PA, Bellin MD, Andersen DK, Bradley D, Cruz-Monserrate Z, Forsmark CE, et al. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer. The lancet Gastroenterology & hepatology. 2016;1(3):226-37.

  • Oeffi nger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, et al. Chronic health conditions in adult survivors of childhood cancer. The New England journal of medicine. 2006;355(15):1572-82.

  • Phillips SM, Padgett LS, Leisenring WM, Stratton KK, Bishop K, Krull KR, et al. Survivors of childhood cancer in the United States: prevalence and burden of morbidity. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2015;24(4):653-63.

  • de Fine Licht S, Rugbjerg K, Gudmundsdottir T, Bonnesen TG, Asdahl PH, Holmqvist AS, et al. Longterm inpatient disease burden in the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study: A cohort study of 21,297 childhood cancer survivors. PLoS medicine. 2017;14(5):e1002296.

  • Mostoufi -Moab S, Seidel K, Leisenring WM, Armstrong GT, Oeffi nger KC, Stovall M, et al. Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. Journal of clinical oncology : offi cial journal of the American Society of Clinical Oncology. 2016;34(27):3240-7.

  • Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ. Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. American journal of epidemiology. 2004;159(12):1160-7.

  • Gallagher EJ, LeRoith D. Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality. Physiological reviews. 2015;95(3):727-48.

  • Liu X, Ji J, Sundquist K, Sundquist J, Hemminki K. The impact of type 2 diabetes mellitus on cancerspecifi c survival: a follow-up study in Sweden. Cancer. 2012;118(5):1353-61.

  • Saydah SH, Loria CM, Eberhardt MS, Brancati FL. Abnormal glucose tolerance and the risk of cancer death in the United States. American journal of epidemiology. 2003;157(12):1092-100

  • Holden SE. Diabetes and Cancer. Endocrine development. 2016;31:135-45.

  • Calzone KA, Soballe PW. Genetic testing for cancer susceptibility. The Surgical clinics of North America. 2008;88(4):705-21, v.

  • Klein AP. Genetic susceptibility to pancreatic cancer. Molecular carcinogenesis. 2012;51(1):14-24.

  • Pierce BL, Austin MA, Ahsan H. Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data. Cancer causes & control : CCC. 2011;22(6):877-83.

  • de Beer JC, Liebenberg L. Does cancer risk increase with HbA1c, independent of diabetes? British journal of cancer. 2014;110(9):2361-8.

  • Xu J, Ye Y, Wu H, Duerksen-Hughes P, Zhang H, Li P, et al. Association between markers of glucose metabolism and risk of colorectal cancer. BMJ open. 2016;6(6):e011430.

  • Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science (New York, NY). 2009;324(5930):1029-33.

  • Adekola K, Rosen ST, Shanmugam M. Glucose transporters in cancer metabolism. Current opinion in oncology. 2012;24(6):650-4.

  • Ryu TY, Park J, Scherer PE. Hyperglycemia as a risk factor for cancer progression. Diabetes & metabolism journal. 2014;38(5):330-6.

  • Machiela MJ, Lindström S, Allen NE, Haiman CA, Albanes D, Barricarte A, et al. Association of type 2 diabetes susceptibility variants with advanced prostate cancer risk in the Breast and Prostate Cancer Cohort Consortium. American journal of epidemiology. 2012;176(12):1121-9.

  • Abe R, Yamagishi S. AGE-RAGE system and carcinogenesis. Current pharmaceutical design. 2008;14(10):940-5.

  • Duan W, Shen X, Lei J, Xu Q, Yu Y, Li R, et al. Hyperglycemia, a neglected factor during cancer progression. BioMed research international. 2014;2014:461917.

  • Ramteke P, Deb A, Shepal V, Bhat MK. Hyperglycemia Associated Metabolic and Molecular Alterations in Cancer Risk, Progression, Treatment, and Mortality. Cancers. 2019;11(9).

  • Han L, Ma Q, Li J, Liu H, Li W, Ma G, et al. High glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. PloS one. 2011;6(11):e27074.

  • Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nature reviews Cancer. 2004;4(8):579-91.

  • Supabphol S, Seubwai W, Wongkham S, Saengboonmee C. High glucose: an emerging association between diabetes mellitus and cancer progression. Journal of molecular medicine (Berlin, Germany). 2021;99(9):1175-93.

  • Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocrine reviews. 2000;21(3):215-44.

  • Yakar S, Pennisi P, Zhao H, Zhang Y, LeRoith D. Circulating IGF-1 and its role in cancer: lessons from the IGF-1 gene deletion (LID) mouse. Novartis Foundation symposium. 2004;262:3-9; discussion -18, 265-8.

  • Crowe FL, Key TJ, Allen NE, Appleby PN, Overvad K, Grønbæk H, et al. A cross-sectional analysis of the associations between adult height, BMI and serum concentrations of IGF-I and IGFBP-1 -2 and -3 in the European Prospective Investigation into Cancer and Nutrition (EPIC). Annals of human biology. 2011;38(2):194-202.

  • Belfi ore A. The role of insulin receptor isoforms and hybrid insulin/IGF-I receptors in human cancer. Current pharmaceutical design. 2007;13(7):671-86.

  • Cox ME, Gleave ME, Zakikhani M, Bell RH, Piura E, Vickers E, et al. Insulin receptor expression by human prostate cancers. The Prostate. 2009;69(1):33-40.

  • Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nature reviews Cancer. 2008;8(12):915-28.

  • LeRoith D, Werner H, Neuenschwander S, Kalebic T, Helman LJ. The role of the insulin-like growth factor-I receptor in cancer. Annals of the New York Academy of Sciences. 1995;766:402-8.57. LeRoith D,

  • Cui Y, Andersen DK. Diabetes and pancreatic cancer. Endocrine-related cancer. 2012;19(5):F9-f26.

  • Hopkins BD, Goncalves MD, Cantley LC. Insulin-PI3K signalling: an evolutionarily insulated metabolic driver of cancer. Nature reviews Endocrinology. 2020;16(5):276-83.

  • Noto H, Goto A, Tsujimoto T, Osame K, Noda M. Latest insights into the risk of cancer in diabetes. Journal of diabetes investigation. 2013;4(3):225-32.

  • Yu T, Robotham JL, Yoon Y. Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(8):2653-8

  • Turturro F, Friday E, Welbourne T. Hyperglycemia regulates thioredoxin-ROS activity through induction of thioredoxin-interacting protein (TXNIP) in metastatic breast cancer-derived cells MDA-MB-231. BMC cancer. 2007;7:96.

  • Othman EM, Leyh A, Stopper H. Insulin mediated DNA damage in mammalian colon cells and human lymphocytes in vitro. Mutation research. 2013;745-746:34-9.

  • Fukada T, Yamasaki S, Nishida K, Murakami M, Hirano T. Zinc homeostasis and signaling in health and diseases: Zinc signaling. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 2011;16(7):1123-34.

  • Rojas A, González I, Morales E, Pérez-Castro R, Romero J, Figueroa H. Diabetes and cancer: Looking at the multiligand/RAGE axis. World journal of diabetes. 2011;2(7):108-13.

  • Zhu B, Qu S. The Relationship Between Diabetes Mellitus and Cancers and Its Underlying Mechanisms. Frontiers in endocrinology. 2022;13:800995.

  • Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW, Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. The New England journal of medicine. 1999;341(15):1097-105.

  • Lengyel E, Makowski L, DiGiovanni J, Kolonin MG. Cancer as a Matter of Fat: The Crosstalk between Adipose Tissue and Tumors. Trends in cancer. 2018;4(5):374-84.

  • Park J, Euhus DM, Scherer PE. Paracrine and endocrine effects of adipose tissue on cancer development and progression. Endocrine reviews. 2011;32(4):550-70.

  • Scully T, Ettela A, LeRoith D, Gallagher EJ. Obesity, Type 2 Diabetes, and Cancer Risk. Frontiers in oncology. 2020;10:615375.

  • Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nature reviews Cancer. 2015;15(8):484-98.

  • Kahn CR, Wang G, Lee KY. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. The Journal of clinical investigation. 2019;129(10):3990-4000.

  • Stern JH, Rutkowski JM, Scherer PE. Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis through Adipose Tissue Crosstalk. Cell metabolism. 2016;23(5):770-84.

  • van Kruijsdijk RC, van der Wall E, Visseren FL. Obesity and cancer: the role of dysfunctional adipose tissue. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2009;18(10):2569-78.

  • Kusminski CM, Bickel PE, Scherer PE. Targeting adipose tissue in the treatment of obesity-associated diabetes. Nature reviews Drug discovery. 2016;15(9):639-60.

  • Guaita-Esteruelas S, Bosquet A, Saavedra P, Gumà J, Girona J, Lam EW, et al. Exogenous FABP4 increases breast cancer cell proliferation and activates the expression of fatty acid transport proteins. Molecular carcinogenesis. 2017;56(1):208-17.

  • Hopkins BD, Goncalves MD, Cantley LC. Obesity and Cancer Mechanisms: Cancer Metabolism. Journal of clinical oncology : offi cial journal of the American Society of Clinical Oncology. 2016;34(35):4277-83.

  • Hu MB, Xu H, Zhu WH, Bai PD, Hu JM, Yang T, et al. High-fat diet-induced adipokine and cytokine alterations promote the progression of prostate cancer in vivo and in vitro. Oncology letters. 2018;15(2):1607- 15.

  • López-Suárez A. Burden of cancer attributable to obesity, type 2 diabetes and associated risk factors. Metabolism: clinical and experimental. 2019;92:136-46.

  • and pro-angiogenic capability of cholangiocarcinoma cells through the miR-122/PKM2 axis. International journal of oncology. 2019;55(1):298-308.

  • Wang WJ, Lai HY, Zhang F, Shen WJ, Chu PY, Liang HY, et al. MCL1 participates in leptin-promoted mitochondrial fusion and contributes to drug resistance in gallbladder cancer. JCI insight. 2021;6(15).

  • Yoon YS, Kwon AR, Lee YK, Oh SW. Circulating adipokines and risk of obesity related cancers: A systematic review and meta-analysis. Obesity research & clinical practice. 2019;13(4):329-39.

  • Zhao C, Wu M, Zeng N, Xiong M, Hu W, Lv W, et al. Cancer-associated adipocytes: emerging supporters in breast cancer. Journal of experimental & clinical cancer research : CR. 2020;39(1):156.

  • Anothaisintawee T, Wiratkapun C, Lerdsitthichai P, Kasamesup V, Wongwaisayawan S, Srinakarin J, et al. Risk factors of breast cancer: a systematic review and meta-analysis. Asia-Pacifi c journal of public health. 2013;25(5):368-87.

  • Goodman-Gruen D, Barrett-Connor E. Sex differences in the association of endogenous sex hormone levels and glucose tolerance status in older men and women. Diabetes care. 2000;23(7):9

  • Carstensen B, Witte DR, Friis S. Cancer occurrence in Danish diabetic patients: duration and insulin effects. Diabetologia. 2012;55(4):948-58.

  • Currie CJ, Poole CD, Gale EA. The infl uence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52(9):1766-77.

  • Hemkens LG, Grouven U, Bender R, Günster C, Gutschmidt S, Selke GW, et al. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia. 2009;52(9):1732-44.

  • Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ (Clinical research ed). 2005;330(7503):1304-5.

  • Sciacca L, Cassarino MF, Genua M, Pandini G, Le Moli R, Squatrito S, et al. Insulin analogues differently activate insulin receptor isoforms and post-receptor signalling. Diabetologia. 2010;53(8):1743-53.

  • Shlomai G, Neel B, LeRoith D, Gallagher EJ. Type 2 Diabetes Mellitus and Cancer: The Role of Pharmacotherapy. Journal of clinical oncology : offi cial journal of the American Society of Clinical Oncology. 2016;34(35):4261-9.

  • Onitilo AA, Engel JM, Glurich I, Stankowski RV, Williams GM, Doi SA. Diabetes and cancer II: role of diabetes medications and infl uence of shared risk factors. Cancer causes & control : CCC. 2012;23(7):991- 1008.

  • Blanquicett C, Roman J, Hart CM. Thiazolidinediones as anti-cancer agents. Cancer therapy. 2008;6(A):25-34

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