Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development

Abstract

Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancerin males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid‘Westernization’ of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumptionof refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigationshave consistently evidenced a significant relationship between obesity-driven inflammation in particular stepsof colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation inobesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines,and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms areaccounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-α (TNF-α). Thesemolecules are secreted by macrophages and are considered as major agents in the transition between acute andchronic inflammation and inflammation-related CRC. The second factor promoting the CRC development inobese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectinin cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transductionpathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR,and 5’AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression).