2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications
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Nieves González1,*, Isabel Prieto2,*, Laura del Puerto-Nevado3,*, Sergio Portal-Nuñez4,*, Juan Antonio Ardura4, Marta Corton5, Beatriz Fernández-Fernández6,7, Oscar Aguilera3, Carmen Gomez-Guerrero6, Sebastián Mas6, Juan Antonio Moreno6, Marta Ruiz-Ortega6, Ana Belen Sanz6,7, Maria Dolores Sanchez-Niño6,7, Federico Rojo8, Fernando Vivanco9, Pedro Esbrit4, Carmen Ayuso5, Gloria Alvarez-Llamas7,9, Jesús Egido1,6, Jesús García-Foncillas3, Alberto Ortiz6,7 and Diabetes Cancer Connect Consortium10
1 Renal, Vascular and Diabetes Research Laboratory, IIS-Fundacion Jimenez Diaz-UAM, Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
2 Radiation Oncology, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
3 Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
4 Bone and Mineral Metabolism laboratory, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
5 Genetics, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
6 Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
7 REDINREN, Madrid, Spain
8 Pathology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
9 Immunology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
10 Membership of the DiabetesCancerConnect Consortium is provided in the Acknowledgments
* These authors have contributed equally to this work
Alberto Ortiz, email:
Keywords: hyperglycemia, inflammation, diabetic kidney disease, colon cancer, diabetes mellitus
Received: September 07, 2016 Accepted: December 26, 2016 Published: January 03, 2017
Worldwide deaths from diabetes mellitus (DM) and colorectal cancer increased by 90% and 57%, respectively, over the past 20 years. The risk of colorectal cancer was estimated to be 27% higher in patients with type 2 DM than in non-diabetic controls. However, there are potential confounders, information from lower income countries is scarce, across the globe there is no correlation between DM prevalence and colorectal cancer incidence and the association has evolved over time, suggesting the impact of additional environmental factors. The clinical relevance of these associations depends on understanding the mechanism involved. Although evidence is limited, insulin use has been associated with increased and metformin with decreased incidence of colorectal cancer. In addition, colorectal cancer shares some cellular and molecular pathways with diabetes target organ damage, exemplified by diabetic kidney disease. These include epithelial cell injury, activation of inflammation and Wnt/β-catenin pathways and iron homeostasis defects, among others. Indeed, some drugs have undergone clinical trials for both cancer and diabetic kidney disease. Genome-wide association studies have identified diabetes-associated genes (e.g. TCF7L2) that may also contribute to colorectal cancer. We review the epidemiological evidence, potential pathophysiological mechanisms and therapeutic implications of the association between DM and colorectal cancer. Further studies should clarify the worldwide association between DM and colorectal cancer, strengthen the biological plausibility of a cause-and-effect relationship through characterization of the molecular pathways involved, search for specific molecular signatures of colorectal cancer under diabetic conditions, and eventually explore DM-specific strategies to prevent or treat colorectal cancer.
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