Role of the Ghrelin System in Colitis and Hepatitis as Risk Factors for Inflammatory-Related Cancers

Abstract

It is not known exactly what leads to the development of colorectal cancer (CRC) and hepatocellular carcinoma (HCC), but there are specific risk factors that increase the probability of their occurrence. The unclear pathogenesis, too-late diagnosis, poor prognosis as a result of high recurrence and metastasis rates, and repeatedly ineffective therapy of both cancers continue to challenge both basic science and practical medicine. The ghrelin system, which is comprised of ghrelin and alternative peptides (e.g., obestatin), growth hormone secretagogue receptors (GHS-Rs), and ghrelin-O-acyl-transferase (GOAT), plays an important role in the physiology and pathology of the gastrointestinal (GI) tract. It promotes various physiological effects, including energy metabolism and amelioration of inflammation. The ghrelin system plays a role in the pathogenesis of inflammatory bowel diseases (IBDs), which are well known risk factors for the development of CRC, as well as inflammatory liver diseases which can trigger the development of HCC. Colitis-associated cancer serves as a prototype of inflammation-associated cancers. Little is known about the role of the ghrelin system in the mechanisms of transformation of chronic inflammation to low- and high-grade dysplasia, and, finally, to CRC. HCC is also associated with chronic inflammation and fibrosis arising from different etiologies, including alcoholic and nonalcoholic fatty liver diseases (NAFLD), and/or hepatitis B (HBV) and hepatitis C virus (HCV) infections. However, the exact role of ghrelin in the progression of the chronic inflammatory lesions into HCC is still unknown. The aim of this review is to summarize findings on the role of the ghrelin system in inflammatory bowel and liver diseases in order to better understand the impact of this system on the development of inflammatory-related cancers, namely CRC and HCC.