Question ID: WS-10
Submitted by: Gerald Denis
January 26, 2011
Cancer, obesity and inflammation Background. ‘Metabolically healthy obese’ (MHO) individuals comprise about 25% of the adult obese population in the US. This population enjoys a significantly reduced risk of complications arising from obesity, such as cardiovascular disease and Type 2 diabetes. Interestingly, they also display a reduced inflammatory profile, including relatively less severe elevation of TNF, CRP, TGFb and other proinflammatory cytokines in the context of their obesity, as well as relatively less severe ablation of protective factors such as adiponectin. Given the well established links between obesity and inflammation, and between inflammation and cancer, it is reasonable to hypothesize that MHO individuals show a reduced incidence of certain obesity-associated cancers, such as colorectal cancer and breast cancer. (Cf. Denis (2010) Discov Med 10: 489-99. PMID: 21189220) Feasibility. Unhealthy obese individuals should be compared to MHO, with regard to SNPs in the genes that encode pro-inflammatory cytokines, or loci implicated in the HLA-associated diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, lupus and Type 1 diabetes). Serum markers of inflammation could be correlated with cancer risk. Biomarkers that define protection from cancer could be deduced from such populations. Implications. For the sake of argument, if human inflammatory responses exhibit a Gaussian distribution, and the MHO population anchors the left hand end, then a symmetric distribution of inflammation implies a right hand end of the population that is more ’pro-inflammatory’ than the mean. Obese individuals at this end of the distribution, accounting for perhaps as many as 10 million Americans, would be predicted to have much greater risk of obesity-associated Type 2 diabetes and cardiovascular disease than the mean, and also to have elevated risk for obesity-associated cancers. At present, biomarkers that identify this at-risk group are unknown, nor are therapeutic options or behavioral interventions identified. NCI should consider developing an RFA to address this question.
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