Obesity and Cancer: Evidence, Postulated Mechanisms and Prospectives

Authors: Hala Fawzy Mohamed Kamel, Hiba Saeed A Bagader Al-Amodi, Mohammed Hasan Mukhtar

Obesity is a major health problem tremendously increasing worldwide, obesity has been accompanied by a state of metabolic dysregulation, characterized by insulin resistance and may be associated with many comorbidities such as metabolic syndrome, type 2 diabetes and cardiovascular complications. Lately a great attention has been gained toward the association of obesity with certain cancers. Numerous studies and meta-analysis reported that, obesity is associated with increased risk of esophageal adenocarcinoma, postmenopausal breast cancer, and endometrial, renal, pancreatic, prostate and colorectal cancers. In spite of, the evidence of such association that link obesity with risk and recurrence or death from cancer, however the linking mechanisms has not been yet fully explained. Obesity may promote cancer by: 1) alteration of adipocytokines: Leptin, adiponectin, resistin and visfatin with promotion of angiogenesis and interactions with other mediators and cytokines. 2) Hypoxia and angiogenesis due to expansion of adipose tissue with release of certain mediators that stimulate angiogenesis. 3) Metaflammation state of low grade and chronic inflammation that merely stimulate release of cytokines as (TNFα) and (IL-6) and the activation of pro-inflammatory signaling. 4) Insulin resistance with hyperinsulinemia and increased levels of insulin and growth factors as IGFs and IGF binding proteins. 5) Increased levels of sex steroids, including estradiol and Dehydroepiandrosterone (DHEA) particularly in cases of endometrial and postmenopausal breast cancers. 6) oxidative stress and reduction of antioxidants with possibility of oxidative damage or mutation of DNA. 7) epigenetic mechanisms, including DNA methylation , histones and chromatin remodeling factors . In fact, it remains unclear how the convergence of these mechanisms may drive obesity-associated cancer, considering the complex and multi-factorial characterization of cancer as well as the variation of genetics background of obese subjects. Prospective studies is worth pursuing especially towards therapeutic implications to prevent or treat obesity- associated cancer. Our aim is providing updated and comprehensive review about postulated and prospective links and molecular mechanisms between obesity and cancer, focusing upon mechanistic mediators that may drive obesity- associated cancers and may be targeted molecules for prospectives therapies. You can submit your Manuscripts at: 

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[v1] 2017-08-26 01:57:38

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