Fernandez CJ, George AS, Subrahmanyan NA, Pappachan JM. Epidemiological link between obesity, type 2 diabetes mellitus and cancer. World J Methodol 2021; 11(3): 23-45 [PMID: 34026577 DOI: 10.5662/wjm.v11.i3.23]
Corresponding Author of This Article
Joseph M Pappachan, MD, FRCP, Consultant, Honorary Professor, Senior Researcher, Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, United Kingdom. drpappachan@yahoo.co.in
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Methodol. May 20, 2021; 11(3): 23-45 Published online May 20, 2021. doi: 10.5662/wjm.v11.i3.23
Epidemiological link between obesity, type 2 diabetes mellitus and cancer
Cornelius J Fernandez, Annu Susan George, Nikhila A Subrahmanyan, Joseph M Pappachan
Cornelius J Fernandez, Department of Endocrinology and Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, United Kingdom
Annu Susan George, Department of Medical Oncology, VPS Lakeshore Hospital, Cochin 682040, India
Nikhila A Subrahmanyan, Department of Internal Medicine, Al-Azhar Medical College, Thodupuzha 685605, India
Joseph M Pappachan, Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
Joseph M Pappachan, Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
Joseph M Pappachan, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom
Author contributions: Fernandez CJ and George AS performed extensive literature review, drafted the initial manuscript, created the pictures and share the first authorship; Subrahmanyan NA added points with additional literature review, help with the pictures and revision; Pappachan JM conceived the idea, inputted additional scientific points especially the obesity and metabolic aspects of the paper, revised the entire work critically, and approved the final version for publication; all the authors contributed to revision of the paper after peer reviews.
Conflict-of-interest statement: Dr. Pappachan and co-authors have nothing to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Joseph M Pappachan, MD, FRCP, Consultant, Honorary Professor, Senior Researcher, Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, United Kingdom. drpappachan@yahoo.co.in
Received: January 13, 2021 Peer-review started: January 13, 2021 First decision: March 1, 2021 Revised: March 2, 2021 Accepted: March 19, 2021 Article in press: March 19, 2021 Published online: May 20, 2021
Abstract
There exists a complex interaction between obesity, type 2 diabetes mellitus (T2DM) and cancer, and an increase in the incidence of cancer is expected with the growing obesity-diabetes pandemic. The association of cancer with diabetes mellitus and obesity appears to be site-specific, the highest risk being for post-menopausal breast cancer, endometrial cancer, and colorectal cancer. Moreover, there is worsening of hyperglycaemia with the onset of cancer, evidencing a bi-directional link between cancer and diabetes mellitus and the need for monitoring for diabetes in cancer survivors. In this review, we look at the epidemiological evidence from observational studies and Mendelian randomization studies linking obesity, diabetes, and cancer, as well as the complex pathophysiological mechanisms involved, including insulin resistance with associated hyperinsulinaemia, the effect of chronic low-grade inflammation, and the effect of various adipokines that are associated with obesity and T2DM. Additionally, we describe the novel therapeutic strategies, based on their role on the discrete pathophysiological mechanisms involved in the tumourigenesis.
Core Tip: Cancer is the second most common cause of death globally, and the complex pathogenic mechanisms in the development of cancer are not yet fully elucidated. The interplay between obesity, type 2 diabetes and some forms of cancer are well known for the past few years. With a steady increase in the obesity and diabetes pandemics, the incidence of cancer is expected to increase exponentially in the coming years. This review discusses the complex pathophysiological mechanisms linking these three major disease entities, to enhance clinician awareness across the globe, and proposes emerging potential therapeutic strategies.
