title: Insight into the impact of diabetes mellitus on the increased risk of hepatocellular carcinoma: mini-review.
abstract: Hepatocellular carcinoma is a multifactorial disease which is associated with a background of many causal risk factors. Diabetes mellitus however is one of the most common co-morbid illnesses found in hepatocellular carcinoma patients that are significantly associated with worsening of hepatocellular carcinoma development, patient prognosis and survival. Therefore, efforts have been focused on understanding the mechanisms underlying progression of hepatocellular carcinoma onset and development especially in diabetic patients. To our knowledge, there are no reports which address the impact of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) along with epigenetic regulations associated with increased risk of hepatocellular carcinoma confounded by diabetes mellitus. Therefore, this mini-review focuses on the possible intermediary mechanisms involved in worsening the onset and progression of hepatocellular carcinoma development confounded by diabetes mellitus. The first approach is to look at the role of inflammatory mediators (TNF-α and IL-6) in apoptosis and inflammation during hepatocarcinogenesis through monitoring levels of apoptotic regulators, B-cell lymphoma 2 protein which is encoded by BCL2 gene and apoptosis regulator BAX known as bcl-2-like protein 4 which is encoded by the BAX gene. The second approach is to focus on the possible epigenomic reprogramming that drives hepatocellular transformation since epigenetic modification of DNA is a key feature in the pathogenesis of hepatocarcinogenesis. Both approaches may suggest role of using Bcl2 and Bax as apoptotic and inflammatory markers for hepatocellular carcinoma detection as well as the importance impact of DNA methylation, hypomethylation or histone modifications as attractive candidates for early-detection biomarkers of hepatocellular carcinoma.
authors.affiliation: Dasman Genome Center, Biomedical Research Department, Dasman Diabetes Institute, Dasman, Kuwait ; Department of Biomedical Research, Genetics and Genomics Unit/Dasman Genome Center, Dasman Diabetes Institute, P.O.Box 1180, Dasman 15462, Kuwait.
authors.forename: Maisa Mahmoud
authors.initials: MM
authors.lastname: Ali Kamkar
authors.affiliation: Immunology and Innovative Cell Therapy Unit, Biomedical Research Department, Dasman Diabetes Institute, Dasman, Kuwait.
authors.forename: Rasheed
authors.initials: R
authors.lastname: Ahmad
authors.affiliation: Dasman Genome Center, Biomedical Research Department, Dasman Diabetes Institute, Dasman, Kuwait.
authors.forename: Osama
authors.initials: O
authors.lastname: Alsmadi
authors.affiliation: Dasman Diabetes Institute, Dasman, Kuwait.
authors.forename: Kazem
authors.initials: K
authors.lastname: Behbehani
keywords: Apoptosis and inflammation; DNA methylation or histone modifications; Diabetes mellitus; Epigenomic reprogramming; Hepatocarcinogenesis; Hepatocellular carcinoma