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Diabetes and Cancer

  • Joanna Krajewska (Wojciechowska)
  • Wojciech Krajewski
  • Tomasz Zatoński
Chapter

Abstract

Diabetes mellitus (DM) and cancers are the leading causes of death worldwide. Recent evidences imply that there is a significant association between DM (mainly type 2 DM) and neoplastic transformation. The presumed links between these two entities are mainly biological linking factors (hyperinsulinemia, 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, the studies on the risk of carcinogenesis in other sites of the human body are also available. Interestingly, antidiabetic 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 antidiabetic medications present antineoplastic features via enhancing the effectiveness of conventional chemotherapy. Antineoplastic 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 antidiabetic drugs on cancer risk and cancer biology.

Keywords

Diabetes mellitus Cancer Antidiabetic drugs Oncogenesis Hyperinsulinemia Hyperglycaemia Obesity 

Notes

Glossary

Hyperinsulinemia

increased serum insulin level

Hyperglycaemia

increased serum glucose level

Pro-neopastic

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 metastasize

Adipokines

adipose tissue polypeptide hormones, e.g. leptin and 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, tumorigenesis, and carcinogenesis

a group of mechanisms leading to transformation of normal cells to cancer cell

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 ability to differentiate into specialized cells and to divide to synthesize more stem cells

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Suggested/Further Reading

  1. 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 Prev Res. 2010;3(11):1451–61. – a systemic review with meta-analysis presenting the inverse association between metformin and cancer risk.CrossRefGoogle Scholar
  2. 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(4):825–36. – another study assessing the influence of anti-diabetic medications on cancer biology.PubMedCrossRefGoogle Scholar
  3. 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. – a clear and comprehensive consensus report on the correlation between diabetes mellitus and oncogenesis.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Pollak M. Potential applications for biguanides in oncology. J Clin Invest. 2013;123(9):3693–700. – a study on potential usefulness of biguanides (metformin with its antineoplastic activities) in oncology.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer. 2015;15(8):484–98. – a study presenting increased risk of cancer incidence in patients with adiposity ( adiposity is significantly correlated with type 2 diabetes mellitus).PubMedCrossRefGoogle Scholar
  6. Ryu TY, Park J, Scherer PE. Hyperglycemia as a risk factor for cancer progression. Diabetes Metab J. 2014;38(5):330–6. – a study explaining the tumor-promoting activity of hyperglycemia.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Joanna Krajewska (Wojciechowska)
    • 1
  • Wojciech Krajewski
    • 2
  • Tomasz Zatoński
    • 1
  1. 1.Department and Clinic of Otolaryngology, Head and Neck SurgeryWrocław Medical UniversityWrocławPoland
  2. 2.Department and Clinic of UrologyWrocław Medical University HospitalWrocławPoland

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