FTO gene, obesity and colon cancer: from epidemiological evidence to laboratory studies

Both epidemiological surveys and laboratory studies have demonstrated that obesity can increase colon cancer incidence and is one of factors leading to poor prognosis. However, the mechanisms for the association of obesity with colon cancer are not well elucidated although both genetic and other cancer risk factors have been reported to play an important role. The fat mass and obesity associated (FTO) gene is the first gene in which a common genetic variant is strongly associated with body mass index (BMI) in the general population. Over-expression of the FTO gene increases food intake, which in turn leads to obesity, one of the major risks to cancer incidences. Furthermore, people with different FTO genotypes show difference not only in the mean value but also in the variance of BMI. Recent studies have shown that genetic mutations in the FTO gene are associated with the carcinogenesis of several cancers including colon cancer. It has also been reported that the FTO-induced increase of cancer incidences is independent of obesity. Mechanistically, this is due to that FTO can activate different intracellular signalling pathways that are relevant to cancer development. Thus, FTO gene is related to the colon cancer incidence either through the obesity-dependent or the obesity-independent mechanism. In this review, we summarize the evidence of FTO being involved in colon carcinogenesis and discuss the possible mechanisms as well as prevention approaches.