Type 2 diabetes and colorectal cancer

Colorectal cancer (CRC) is the third most commonly detected cancer worldwide. Rising CRC incidence trends are chiefly regarded as a result of the fast ‘Westernization’ of life-style and are associated withcalorically extra high-fat/low-fiber diet, consumption of refined products, lack of exercise, and obesity. A positive association between type 2 diabetes and risk of colorectal cancer (27% higher in patients with type 2 DM) has been reported. Type 2 diabetes may result in epithelial cell injury, Wnt/β-catenin pathways, iron homeostasis defects, altered adipokine concentrations (leptin and adiponectin),abnormal carbohydrate and lipid metabolism, high levels of circulating insulin, insulin growth factor-1, as well as chronic inflammation and increased inflammatory factors including TGFβ, NFKB, TNFαand ROS. All these factors could lead to the alteration of energy sensing pathways such as the AMP activated kinase (PRKA), mechanistic (mammalian) target of rapamycin (mTOR), SIRT1, JAK/STAT,MAPK and autophagy signaling pathways. Moreover, these pathways may couple metabolic and epigenetic alterations which are central to oncogenic transformation. In spite of the limited evidence, some diabetes drugs (e.g. metformin) have been associated with decreased incidence of CRC. In addition, genome-wide association studies have identified diabetes-associated genes (e.g. TCF7L2) that may also contribute to CRC. Further studies should elucidate the worldwide association between DM and CRC, strengthen the biological possibility of a cause-and-effect relation through characterization of the molecular pathways comprised, search for specific molecular signatures of CRC under diabetic conditions, and finally probe DM-specific strategies to prevent or treat CRC

کلیدواژه ها:

Colorectal Cancer ، Cancer Prevention ، Gene and Cancer ، Cancer Risks ، Lifestyle and Cancer ، Cancer Genetics