title: 2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications.
abstract: 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.
authors.affiliation: Renal, Vascular and Diabetes Research Laboratory, IIS-Fundacion Jimenez Diaz-UAM, Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: Nieves
authors.initials: N
authors.lastname: González
authors.affiliation: Radiation Oncology, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Prieto
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Del Puerto-Nevado
authors.affiliation: Bone and Mineral Metabolism laboratory, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Portal-Nuñez
authors.affiliation: Bone and Mineral Metabolism laboratory, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Ardura
authors.affiliation: Genetics, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Corton
authors.affiliation: Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.|REDINREN, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Fernández-Fernández
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Aguilera
authors.affiliation: Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gomez-Guerrero
authors.affiliation: Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Mas
authors.affiliation: Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Moreno
authors.affiliation: Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.affiliation: Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.|REDINREN, Madrid, Spain.
authors.forename: Ana Belen
authors.initials: AB
authors.lastname: Sanz
authors.affiliation: Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.|REDINREN, Madrid, Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Sanchez-Niño
authors.affiliation: Pathology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
authors.affiliation: Immunology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Vivanco
authors.affiliation: Bone and Mineral Metabolism laboratory, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Esbrit
authors.affiliation: Genetics, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.affiliation: REDINREN, Madrid, Spain.|Immunology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Alvarez-Llamas
authors.affiliation: Renal, Vascular and Diabetes Research Laboratory, IIS-Fundacion Jimenez Diaz-UAM, Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.|Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Foncillas
authors.affiliation: Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain.|REDINREN, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents
keywords: colon cancer; diabetes mellitus; diabetic kidney disease; hyperglycemia; inflammation