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World J Gastroenterol. Jul 21, 2014; 20(27): 8939-8946
Published online Jul 21, 2014. doi: 10.3748/wjg.v20.i27.8939
Chemoprevention of colorectal cancer by targeting obesity-related metabolic abnormalities
Yohei Shirakami, Masahito Shimizu, Masaya Kubota, Hiroshi Araki, Takuji Tanaka, Hisataka Moriwaki, Mitsuru Seishima
Yohei Shirakami, Mitsuru Seishima, Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
Masahito Shimizu, Masaya Kubota, Hiroshi Araki, Hisataka Moriwaki, Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
Takuji Tanaka, Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
Author contributions: Shirakami Y performed the review of the literature and wrote the paper; Shimizu M and Tanaka T performed the review of the literature and edited the final draft; Kubota M and Araki H created the figures used in this review; Moriwaki H and Seishima M gave the final approval of the version to be published.
Correspondence to: Masahito Shimizu, MD, PhD, Department of Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. shimim-gif@umin.ac.jp
Telephone: +81-58-2306313 Fax: +81-58-2306310
Received: September 27, 2013
Revised: December 20, 2013
Accepted: April 1, 2014
Published online: July 21, 2014
Abstract

Obesity and its related metabolic disorders, including insulin resistance and chronic inflammation, increase the risk of colorectal cancer (CRC). This observation suggests that the metabolic abnormalities associated with obesity can be effective targets for preventing the development of CRC in obese individuals. In recent years, many studies using obese and diabetic animal models have been conducted to investigate the chemoprevention of CRC using pharmaceutical or nutritional interventions. Pitavastatin, a medicine used to treat hyperlipidemia, prevents the development of obesity-related colorectal carcinogenesis by attenuating chronic inflammation. Anti-hypertensive medicines, such as captopril and telmisartan, also suppress the formation of colonic preneoplastic lesions in obese and diabetic mice. In addition, several phytochemicals, including green tea catechins, have been reported to improve metabolic disorders and prevent the development of various cancers, including CRC. Moreover, the administration of branched-chain amino acids, which improves protein malnutrition and prevents the progression of hepatic failure, is effective for suppressing obesity-related colon carcinogenesis, which is thought to be associated with improvements in insulin resistance. In the present article, we summarize the detailed relationship between metabolic abnormalities and the development of CRC. This review also outlines recent evidence, in particular drawing from basic and clinical examinations using either pharmaceutical or nutritional intervention that suggests that targeting metabolic alterations may be an effective strategy for preventing the development of CRC in obese individuals.

Keywords: Colorectal cancer, Obesity, Green tea catechin, Branched-chain amino acid, Chemoprevention

Core tip: Obesity and its related metabolic disorders increase the risk of colorectal cancer (CRC). Many studies using obese animal models have been conducted to investigate the chemoprevention of CRC using pharmaceutical or nutritional interventions. Lipid-lowering and anti-hypertensive medicines suppress the development of colonic preneoplastic lesions in obese mice. Green tea catechins improve metabolic disorders and prevent the development of CRC. The administration of branched-chain amino acids may be effective for suppressing obesity-related CRC. This review summarizes recent evidence that suggests that targeting metabolic alterations may be an effective strategy for preventing the development of CRC in obese individuals.