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Diabetes and Cancer

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Abstract

Diabetes mellitus (DM) and cancers are leading causes of death worldwide. Recent evidence implies a significant association between DM (mainly type 2 DM) and neoplastic transformation. The presumed links between these two entities are mainly biological linking factors (hyperinsulinaemia, hyperglycaemia and chronic inflammation caused by excessive adipose tissue). The increased risk of oncogenesis was observed mainly for pancreatic and liver cancers, cancers of the genitourinary system and breast cancer. Nevertheless, studies on the risk of carcinogenesis in other sites of human body are also available. Interestingly, anti-diabetic drugs also influence the chance of neoplastic transformation. Some of them presumably elevate the risk of oncogenesis, some reduce the risk and some express inconsistent activity. It was also revealed that several anti-diabetic medications present anti-neoplastic features via enhancing the effectiveness of conventional chemotherapy. Anti-neoplastic activities of metformin and its ability to prevent metastasis are widely discussed in the literature. This chapter summarizes the current knowledge of the correlation between diabetes mellitus and oncogenesis. It also discusses the influence of anti-diabetic drugs on cancer risk and cancer biology.

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Further Reading

  • Decensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A, Bonanni B, et al. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prevent Res. 2010;3:1451–61. A systemic review with meta-analysis presenting the inverse association between metformin and cancer risk

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  • Feng YH, Velazquez-Torres G, Gully C, Chen J, Lee MH, Yeung SC. The impact of type 2 diabetes and antidiabetic drugs on cancer cell growth. J Cell Mol Med. 2011;15:825–36. Another study assessing the influence of anti-diabetic medications on cancer biology

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  • Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33:1674–85. A clear and comprehensive consensus report on the correlation between diabetes mellitus and oncogenesis

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  • Pollak M. Potential applications for biguanides in oncology. J Clin Invest. 2013;123:3693–700. A study on potential usefulness of biguanides (metformin with its antineoplastic activities) in oncology

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer. 2015;15:484–98. A study presenting increased risk of cancer incidence in patients with adiposity ( adiposity is significantly correlated with type 2 diabetes mellitus)

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  • Ryu TY, Park J, Scherer PE. Hyperglycemia as a risk factor for cancer progression. Diabetes Metab J. 2014;38:330–6. A study explaining the tumor-promoting activity of hyperglycemia

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  • Tsilidis KK, Kasimis JC, Lopez DS, Ntzani EE, Ioannidis JP. Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ. 2015;350:g7607. A comprehensive meta-analysis on the correlation between type 2 diabetes mellitus and cancer

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  • Wojciechowska J, Krajewski W, Bolanowski M, Krecicki T, Zatonski T. Diabetes and Cancer: a Review of Current Knowledge. Exp Clin Endocrinol Diabetes. 2016;124(5):263–75. A review article written by the authors of this chapter. The chapter is based on this article. The article, similarly to this chapter, analyse the association between diabetes mellitus (mainly type 2 diabetes mellitus) and cancer risk and cancer biology. The article also present the association between diabetes mellitus and antidiabetic medications

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  • Wu L, Zhu J, Prokop LJ, Murad MH. Pharmacologic therapy of diabetes and overall cancer risk and mortality: a meta-analysis of 265 studies. Sci Rep. 2015;5:10147. A meta-analysis assessing the association between anti-diabetic pharmacotherapy and cancer risk and mortality

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Author information

Authors and Affiliations

  1. Department and Clinic of Otolaryngology, Head and Neck Surgery, Wrocław Medical University Hospital, Wrocław, Poland

    Joanna Wojciechowska, Wojciech Krajewski & Tomasz Zatoński

  2. Department and Clinic of Urology, Wrocław Medical University Hospital, Wrocław, Poland

    Wojciech Krajewski

  3. Multidisciplinary Diabetes Center Mexico, Ciudad de México, Mexico

    Joel Rodriguez-Saldana

Authors
  1. Joanna Wojciechowska
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  2. Wojciech Krajewski
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  3. Tomasz Zatoński
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  4. Joel Rodriguez-Saldana
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Editor information

Editors and Affiliations

  1. Mexico City, Mexico

    Joel Rodriguez-Saldana

Glossary

Hyperinsulinaemia

Increased serum insulin level.

Hyperglycaemia

Increased serum glucose level.

Pro-neoplastic

Promoting neoplastic transformation.

PI3K/Akt/mTOR signalling pathway (phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signalling pathway)—

Critical pathway in oncogenesis.

IGF-binding proteins

Proteins crucial in IGF serum transfer and bioavailability.

Urokinase plasminogen activator (uPA)

A critical mediator in cancer cell displacement.

ETM (Epithelial to Mesenchymal Transition process)

A mechanism that enables cancer cells to metastasise.

Adipokines

Adipose tissue polypeptide hormones, e.g. leptin, adiponectin.

SNPs (Single Nucleotide Polymorphisms)

A sequence in a single nucleotide that is observed at a specific position in the genome.

NAFLD (non-alcoholic fatty liver disease)

A condition of fat deposits accumulation not induced by alcohol abuse. NAFLD is associated with metabolic syndrome and insulin resistance.

Lipotoxicity

Malfunction or death of non-adipose tissue cells caused by accumulation of excessive lipids.

Oxidative stress

Imbalance between antioxidant and prooxidant factors.

Oncogenesis, tumourigenesis, carcinogenesis

A group of mechanisms leading to transformation of normal cells to cancer cells.

Milieu

A setting in which something happens (environment, surrounding).

Gluconeogenesis

A process of glucose biosynthesis.

Glycogenolysis

A process of biochemical degradation of glycogen to glucose.

NF-κB

A factor controlling transcription of DNA and cells survival.

OVCAR

Epithelial ovarian cancer cell lines.

Stem cell

Undifferentiated cells which have the ability to differentiate into specialized cells, and to divide to synthesize more stem cells.

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Wojciechowska, J., Krajewski, W., Zatoński, T., Rodriguez-Saldana, J. (2023). Diabetes and Cancer. In: Rodriguez-Saldana, J. (eds) The Diabetes Textbook. Springer, Cham. https://doi.org/10.1007/978-3-031-25519-9_63

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