Diabetes and cancer

Vigneri, Paolo; Frasca, Francesco; Sciacca, Laura; Pandini, Giuseppe; Vigneri, Riccardo

doi:10.1677/erc-09-0087

Cited by 1,009Metabolism, Diabetes, and CancerCancer Risks and FactorsGrowth Hormone and Insulin-like Growth Factors

Diabetes and cancer

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Vigneri, Paolo, Frasca, Francesco, Sciacca, Laura, Pandini, Giuseppe, Vigneri, Riccardo·2009·Endocrine Related Cancer

DOI 10.1677/erc-09-0087

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Abstract

Diabetes and cancer are two heterogeneous, multifactorial, severe, and chronic diseases. Because of their frequency, reciprocal influences - even minor influences - may have a major impact. Epidemiological studies clearly indicate that the risk of several types of cancer (including pancreas, liver, breast, colorectal, urinary tract, and female reproductive organs) is increased in diabetic patients. Mortality is also moderately increased. Several confounding factors, having general or site-specific relevance, make it difficult to accurately assess cancer risk in diabetic patients. These factors include diabetes duration, varying levels of metabolic control, different drugs used for therapy, and the possible presence of chronic complications. Hyperinsulinemia most likely favors cancer in diabetic patients as insulin is a growth factor with pre-eminent metabolic but also mitogenic effects, and its action in malignant cells is favored by mechanisms acting at both the receptor and post-receptor level. Obesity, hyperglycemia, and increased oxidative stress may also contribute to increased cancer risk in diabetes. While anti-diabetic drugs have a minor influence on cancer risk (except perhaps the biguanide metformin that apparently reduces the risk), drugs used to treat cancer may either cause diabetes or worsen a pre-existing diabetes. In addition to the well-known diabetogenic effect of glucocorticoids and anti-androgens, an increasing number of targeted anti-cancer molecules may interfere with glucose metabolism acting at different levels on the signaling substrates shared by IGF-I and insulin receptors. In conclusion, diabetes and cancer have a complex relationship that requires more clinical attention and better-designed studies.

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Diabetes is associated with reduced risk of prostate cancer.
“Diabetes is associated with reduced risk of prostate cancer.”
From Diabetes and Cancer (2010) · cites this paper as [6]
Diabetes (primarily type 2) is associated with increased risk for some cancers: liver, pancreas, endometrium, colon and rectum, breast, and bladder.
“Diabetes (primarily type 2) is associated with increased risk for some cancers (liver, pancreas, endometrium, colon and rectum, breast, bladder).”
From Diabetes and Cancer (2010) · cites this paper as [6]
Epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer.
“Epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer.”
From Diabetes and Cancer (2010) · cites this paper as [6]
For some other cancer sites there appears to be no association or the evidence is inconclusive.
“For some other cancer sites there appears to be no association or the evidence is inconclusive.”
From Diabetes and Cancer (2010) · cites this paper as [6]
Other cancers (e.g., lung) do not appear to be associated with an increased risk in diabetes, and the evidence for others (e.g., kidney, non-Hodgkin lymphoma) is inconclusive.
“Other cancers (e.g., lung) do not appear to be associated with an increased risk in diabetes, and the evidence for others (e.g., kidney, non-Hodgkin lymphoma) is inconclusive.”
From Diabetes and Cancer (2010) · cites this paper as [6]

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“…and sitagliptin apparently significantly reduced the odds ratios of some special cancers, such as lung cancer, prostate cancer, lymphoma/multiple myeloma for exenatide, and colon cancer and prostate cancer for sitagliptin (Vigneri et al., 2009; Koehler et al., 2011; Nauck and Friedrich, 2013).”
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Epidemiology of prostate cancer in Asian countries
Kimura, T., & Egawa, S. (2018) · International Journal of Urology · doi:10.1111/iju.13593 · Cited by 413 · see citing works
Mortality After Incident Cancer in People With and Without Type 2 Diabetes
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“Cancers most commonly associated with diabetes are those of the pancreas, liver, endometrium, breast, colon, and bladder, while notably, prostate cancer has an inverse association with diabetes (2).”
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“Retrospective studies show that metformin, which reduces hyperinsulinemia, may lower pancreatic cancer risk in animals [292] and in patients by up to 60% [182,293-297], although the magnitude of this effect is controversial [298,299] and it is unclear whether metformin acts via lowering insulin or modulating AMP-activ…”
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Metformin Amplifies Chemotherapy-Induced AMPK Activation and Antitumoral Growth
Rocha, G. Z., Dias, M. M., Ropelle, E. R., Osório–Costa, F., Rossato, F. A., Vercesi, A. E., Saad, M. J. A., & Carvalheira, J. B. C. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2243 · Cited by 305 · see citing works
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“Relationship With Diabetes Mellitus: Epidemiology Patients with DM have an increased risk for developing cancer in several organs and tissues, as well as an increase in cancer mortality, compared to subjects without DM (316).”
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Diabetes and cancer: two diseases with obesity as a common risk factor
Garg, S. K., Maurer, H., Reed, K., & SELAGAMSETTY, R. (2013) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12124 · Cited by 274 · see citing works
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Cancer incidence in Spain, 2015
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Insulin, insulin receptors, and cancer
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Diabetes Mellitus as a Risk Factor for Open-Angle Glaucoma: A Systematic Review and Meta-Analysis
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Chronic Diabetes Complications: The Need to Move beyond Classical Concepts
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Insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R) signaling systems: novel treatment strategies for cancer
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Diabetes Mellitus and the Incidence of Colorectal Cancer: An Updated Systematic Review and Meta-Analysis
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Metformin Inhibits Growth of Thyroid Carcinoma Cells, Suppresses Self-Renewal of Derived Cancer Stem Cells, and Potentiates the Effect of Chemotherapeutic Agents
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PGC1α Promotes Tumor Growth by Inducing Gene Expression Programs Supporting Lipogenesis
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Hyperglycemia, tumorigenesis, and chronic inflammation
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Effects of hyperglycemia on the progression of tumor diseases
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Metformin and Sulfonylureas in Relation to Cancer Risk in Type II Diabetes Patients: A Meta-analysis using primary data of published studies
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Cohort profile: Risk evaluation of cancers in C hinese diabetic individuals: a longitudinal ( REACTION ) study (队列简介：中国糖尿病患者肿瘤发生风险的纵向研究（REACTION研究）)
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Cancer incidence in persons with type 1 diabetes: A five-country study of 9,000 cancers in type 1 diabetic individuals
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Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo
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Risk of Cancer Following Hospitalization for Type 2 Diabetes
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Evaluation of metformin in early breast cancer: a modification of the traditional paradigm for clinical testing of anti-cancer agents
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“Both type 2 diabetes and hyperinsulinemia have been associated with increased breast cancer risk in epidemiologic studies [ 18 ].”
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Genetics of type 2 diabetes: pathophysiologic and clinical relevance
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Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias
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“The risk of endometrial cancer appears to be doubled in women with diabetes [1, 2].”
BackgroundResultInfluential
Prevalence of Diabetes Mellitus in Pancreatic Cancer Compared to Common Cancers
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The cellular and molecular mechanisms by which insulin influences breast cancer risk and progression
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Animal models for type 1 and type 2 diabetes: advantages and limitations
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“In addition, diabetes has also been associated with increased risk of certain cancers and is a recognized risk factor for mental disorders, such as Alzheimer ’ s disease (6, 7).”
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Metformin: An anti-diabetic drug to fight cancer
Daugan, M. V., Wojcicki, A. D., d’Hayer, B., & Boudy, V. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.10.006 · Cited by 166 · see citing works
High Glucose Promotes Pancreatic Cancer Cell Proliferation via the Induction of EGF Expression and Transactivation of EGFR
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Incidence of Diabetes After Cancer Development
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Diabetes and cancer: Epidemiological and biological links
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Metformin and cancer
Rizos, C. V., & Elisaf, M. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.02.038 · Cited by 154 · see citing works
The effect of environmental chemicals on the tumor microenvironment
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“In particular, subjects with type 2 diabetes mellitus are at increased risk of a wide range of malignancies, including breast, endometrial, bladder, kidney, colorectal, pancreatic and liver cancer, as well as hematologic malignancies such as non-Hodgkin’s lymphoma (132), whereas the risk of prostate cancer is reduced…”
Background
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Garrett, C. R., Hassabo, H. M., Bhadkamkar, N. A., Wen, S., Baladandayuthapani, V., Kee, B. K., Eng, C., & Hassan, M. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.71 · Cited by 151 · see citing works
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BackgroundInfluential
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Frequency and Circadian Timing of Eating May Influence Biomarkers of Inflammation and Insulin Resistance Associated with Breast Cancer Risk
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“[9] P.”
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Diabetes and cancer: Associations, mechanisms, and implications for medical practice
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Chronic inflammation and cancer; the two sides of a coin
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Diabetes and Risk of Cancer
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Diabetes and Risk of Prostate Cancer
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“Decreased rates of prostate cancer and NMSC have been reported in the literature [12, 13] and also found in the present study.”
Result
High glucose levels boost the aggressiveness of highly metastatic cholangiocarcinoma cells via O-GlcNAcylation
Phoomak, C., Vaeteewoottacharn, K., Silsirivanit, A., Saengboonmee, C., Seubwai, W., Sawanyawisuth, K., Wongkham, C., & Wongkham, S. (2017) · Scientific Reports · doi:10.1038/srep43842 · Cited by 120 · see citing works
Diabetes and Cancer: Is Diabetes Causally Related to Cancer?
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Authors: Vigneri, P., Frasca, F., Sciacca, L., Pandini, G., & Vigneri, R.
Affiliations: Section of General Pathology 1
University of Catania (IT)
Corresponding author: Vigneri, Paolo
ORCID: Vigneri, Paolo
Frasca, Francesco
Sciacca, Laura
Pandini, Giuseppe
Vigneri, Riccardo
Venue: Endocrine Related Cancer
Publisher: Bioscientifica
Published: 2009-12-01
Volume: 16
Issue: 4
Pages: 1103-1123
ISSN: 1351-0088 (ISSN-L)
1479-6821
DOI: 10.1677/erc-09-0087
OpenAlex: W2163691729
Cited by: 1,009
References: 183
Citations by year: 2026: 20 · 2025: 43 · 2024: 54 · 2023: 49 · 2022: 49 · 2021: 46 · 2020: 50 · 2019: 57 · 2018: 60 · 2017: 75 · 2016: 59 · 2015: 68 · 2014: 85 · 2013: 97 · 2012: 80
FWCI: 5.00
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Endocrine Related Cancer (publishedVersion)
PubMed (publishedVersion)
Funders: Associazione Italiana per la Ricerca sul Cancro
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Oncology › Cancer Risks and Factors
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords: diabetes mellitus, cancer risk, hyperinsulinemia, insulin-like growth factor I, insulin receptor, metformin, antidiabetic drugs, glucocorticoids, androgen receptor antagonists, obesity, hyperglycemia, oxidative stress, pancreatic cancer, liver cancer, breast cancer, colorectal cancer, cancer mortality, confounding factors
MeSH terms: Humans, Neoplasms, Risk Factors, Survival Rate, Diabetes Complications

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