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World J Gastroenterol. Feb 21, 2014; 20(7): 1701-1711
Published online Feb 21, 2014. doi: 10.3748/wjg.v20.i7.1701
Diabetes and gastric cancer: The potential links
Chin-Hsiao Tseng, Farn-Hsuan Tseng
Chin-Hsiao Tseng, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 100, Taiwan
Chin-Hsiao Tseng, Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
Farn-Hsuan Tseng, Dana and David Dornsife College of Letters, Arts and Sciences, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90007, United States
Author contributions: Tseng CH designed study and finalized the paper; and Tseng FH searched literature and wrote the first draft.
Correspondence to: Chin-Hsiao Tseng, MD, PhD, Professor, Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 100, Taiwan. ccktsh@ms6.hinet.net
Telephone: +886-2-23883578 Fax: +886-2-23883578
Received: October 21, 2013
Revised: November 18, 2013
Accepted: December 5, 2013
Published online: February 21, 2014
Abstract

This article reviews the epidemiological evidence linking diabetes and gastric cancer and discusses some of the potential mechanisms, confounders and biases in the evaluation of such an association. Findings from four meta-analyses published from 2011 to 2013 suggest a positive link, which may be more remarkable in females and in the Asian populations. Putative mechanisms may involve shared risk factors, hyperglycemia, Helicobacter pylori (H. pylori) infection, high salt intake, medications and comorbidities. Diabetes may increase the risk of gastric cancer through shared risk factors including obesity, insulin resistance, hyperinsulinemia and smoking. Hyperglycemia, even before the clinical diagnosis of diabetes, may predict gastric cancer in some epidemiological studies, which is supported by in vitro, and in vivo studies. Patients with diabetes may also have a higher risk of gastric cancer through the higher infection rate, lower eradication rate and higher reinfection rate of H. pylori. High salt intake can act synergistically with H. pylori infection in the induction of gastric cancer. Whether a higher risk of gastric cancer in patients with diabetes may be ascribed to a higher intake of salt due to the loss of taste sensation awaits further investigation. The use of medications such as insulin, metformin, sulfonylureas, aspirin, statins and antibiotics may also influence the risk of gastric cancer, but most of them have not been extensively studied. Comorbidities may affect the development of gastric cancer through the use of medications and changes in lifestyle, dietary intake, and the metabolism of drugs. Finally, a potential detection bias related to gastrointestinal symptoms more commonly seen in patients with diabetes and with multiple comorbidities should be pointed out. Taking into account the inconsistent findings and the potential confounders and detection bias in previous epidemiological studies, it is expected that there are still more to be explored for the clarification of the association between diabetes and gastric cancer.

Keywords: Diabetes mellitus, Gastric cancer, Epidemiology, Meta-analysis, Literature review

Core tip: Epidemiological studies suggested a possible higher risk of gastric cancer in patients with diabetes. This article summarizes the findings in four meta-analyses and proposes some mechanisms explaining the association. Findings in the meta-analyses suggested that the association between diabetes and gastric cancer is more remarkable in females and in the Asian populations. Although the mechanisms for such a link remain to be explored, these may involve shared risk factors between diabetes and gastric cancer (such as obesity, insulin resistance, hyperinsulinemia and smoking), hyperglycemia, Helicobacter pylori infection, high salt intake, medications and comorbidities.