Abstract

The global deaths due to colorectal cancer and diabetes mellitus have increased by 57% and 90%, respectively. The relationship between various cancers and diabetes mellitus has been shown in multiple epidemiological studies. Hence, better management of diabetes mellitus is expected to reduce the risk of various cancers. This review focuses on colorectal cancer and aims to summarize recent findings on the antitumor effects of various oral hypoglycemic drugs on colorectal cancer and their estimated mechanisms. Of the seven classes of oral hypoglycemic agents, only metformin was found to have suppressive effects on colorectal cancer in both clinical and basic research. Clinical and basic researches on suppressing effects of glinides, dipeptidyl peptidase-4 inhibitors, thiazolidinedione, α-glucosidase inhibitors, and sodium glucose cotransporter-2 inhibitors against colon carcinogenesis have been insufficient and have not arrived at any conclusion. Therefore, further research regarding these agents is warranted. In addition, the suppressive effects of these agents in healthy subjects without diabetes should also be investigated.

Highlights

  • The global deaths due to colorectal cancer (CRC) and diabetes mellitus (DM) have increased by 57% and 90%, respectively

  • CRC is not caused by a single genetic abnormality, its predominant mechanism has been the multistep carcinogenesis theory, which states that colon cancer develops by the accumulation of multiple gene abnormalities [30]

  • Accumulation of genomic abnormalities in CRC is classified into two types: chromosomal instability (CIN) which is accompanied by structural change of the chromosome and microsatellite instability (MIN) which is caused due to an abnormal repetitive sequence of DNA in the genome without any structural change in chromosome

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Summary

Introduction

The global deaths due to colorectal cancer (CRC) and diabetes mellitus (DM) have increased by 57% and 90%, respectively. The risk of CRC was estimated to be 27% higher in type 2 DM patients than in non-diabetic patients. The number of cases of DM, especially type 2 DM, is increasing, and this trend is expected to continue in the future [1]. Studies that acknowledge the carcinogenesis-inhibiting effect of several oral hypoglycemic agents currently in clinical use have increased in recent years. This review focuses on CRC and aims to summarize the recent findings regarding the antitumor effect of various oral glycemic drugs on CRC and their estimated underlying mechanisms

Diabetes Mellitus
Colorectal Cancer
Epidemiological Relevance of Diabetes Mellitus and Colorectal Cancer Risk
The Insulin-like Growth Factor Signaling System
The Wnt Signaling System
Glucagon-like Peptide-1
Gut Microbiota
Types of Oral Hypoglycemic Drugs for Type 2 Diabetes Mellitus
Sulfonylureas
DPP-4 Inhibitors
Biguanides
Thiazolidinedione
SGLT2 Inhibitors
Findings
Conclusions

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