Review
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World J Gastroenterol. Jan 28, 2011; 17(4): 444-448
Published online Jan 28, 2011. doi: 10.3748/wjg.v17.i4.444
Is diabetes a causal agent for colorectal cancer? Pathophysiological and molecular mechanisms
Olga Giouleme, Michael D Diamantidis, Marios G Katsaros
Olga Giouleme, Michael D Diamantidis, Marios G Katsaros, Department of Gastroenterology, First Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA General Hospital, 546 36, Thessaloniki, Greece
Author contributions: Giouleme O and Diamantidis MD contributed equally to this work; Giouleme O performed the research, analyzed the data and wrote the manuscript; Diamantidis MD performed the research, analyzed the data and wrote the manuscript; Katsaros MG assisted in writing parts of the paper.
Correspondence to: Olga Giouleme, MD, PhD, Assistant Professor, Department of Gastroenterology, First Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA General Hospital, 1 S. Kiriakidi St, 546 36, Thessaloniki, Greece. olgagiouleme@yahoo.gr
Telephone: +30-2310-994687 Fax: +30-2310-994687
Received: March 15, 2010
Revised: April 24, 2010
Accepted: May 1, 2010
Published online: January 28, 2011
Abstract

The possible relationship between diabetes mellitus (DM) and colorectal cancer (CRC), concerning pathophysiological and molecular mechanisms is highlighted in this review. The most recent and complete articles and developments in this particular field were thoroughly reviewed. Common risk factors, such as obesity, sedentary lifestyle, and Western diet between DM and CRC, led to the theory that DM might be a causal agent for CRC development. Various studies have connected type 2 DM and CRC, either proximal or distal, in both sexes. Additionally, chronic insulin treatment has been linked with increased colorectal tumor risk among type 2 diabetic patients. Interestingly, elevated hemoglobin A1c has been proven to be an independent predictor of aggressive clinical behavior in CRC patients. These mechanisms include the insulin-like growth factor-hyperinsulinemia theory and the participation of oncogenic intracellular signaling pathways. Furthermore, it has been proposed that Cox-2 inhibitors might have a role in decreasing the incidence of CRC. Finally, the use of statins to reduce the risk for colon cancer in patients with diabetes has remained controversial. Diabetic patients over 50 should receive counseling regarding their elevated risk for CRC, and screening colonoscopy should be recommended before initiating insulin therapy. However, there are no current guidelines, and this strategy is not yet applicable to some countries, as the corresponding risk would not allow screening colonoscopy to be adopted. There is strong evidence to indicate that DM is a causal agent for CRC development. This conclusion provides new impetus for re-evaluating CRC screening worldwide.

Keywords: Diabetes mellitus; Colorectal cancer; Molecular oncogenic pathways; Screening