Executive Summary : | Colorectal cancer (CRC) is a major global public health issue, influenced by various risk factors such as lifestyle choices and diet. Alcohol consumption is associated with an increased risk of developing CRC, with chronic inflammation playing a crucial role. Alcohol consumption activates pro-inflammatory responses, including the absorption of bacterial endotoxins, infiltration of neutrophils, and inhibition of T-cell function. Long-term alcohol use has been linked to serious medical conditions, including cardiovascular disease, hypertension, digestive complications, and various types of cancer. The intestinal tight junction (TJ) regulates the movement of allergens, toxins, and molecules between cells, and maintains cell polarity. Inflammatory bowel diseases (IBD) exhibit impaired TJs, increased intestinal permeability, and the release of endotoxins into the bloodstream, triggering inflammation. Alcohol consumption disrupts the integrity of TJs, resulting in elevated permeability and reduced expression and localization of colonic junctional TJs. Alcohol opens the TRPV6 channel and increases intracellular calcium levels, while downregulating the expression of defensins, disrupting the gut microbiota and leading to dysbiosis. The interplay between decreased defensin levels caused by alcohol and subsequent alterations in TRPV6 expression may significantly contribute to the progression of CRC. The precise involvement of the TRPV6 channel in colon cancer development and its signaling mechanisms is not yet fully understood. This project aims to investigate the role of the TRPV6 channel in alcohol-induced colorectal cancer and evaluate the effects of a TRPV6 blocker in mitigating CRC progression. |