Obesity: a perfect storm for carcinogenesis

Review of litterature. Obesity-related cancers account for 40% of the cancer cases observed in the USA and obesity is overtaking smoking as the most widespread modifable risk factor for carcinogenesis. Here, we use the hallmarks of cancer framework to delineate how obesity might infuence the carcinogenic hallmarks in somatic cells. We discuss the efects of obesity on (a) sustain ing proliferative signaling; (b) evading growth suppressors; (c) resisting cell death; (d) enabling replicative immortality; (e) inducing angiogenesis; (f) activating invasion and metastasis; (g) reprogramming energy metabolism; and (h) avoiding immune destruction, together with its efects on genome instability and tumour-promoting infammation. We present the current understanding and controversies in this evolving feld, and highlight some areas in need of further cross-disciplinary focus. For instance, the relative importance of the many potentially causative obesity-related factors is unclear for each type of malignancy. Even within a single tumour type, it is currently unknown whether one obesity-related factor consistently plays a predominant role, or if this varies between patients or, even in a single patient with time. Clarifying how the hallmarks are afected by obesity may lead to novel prevention and treatment strategies for the increasingly obese population.