Unraveling the Complex Interactions between the Fat Mass and Obesity-Associated (FTO) Gene, Lifestyle, and Cancer.

Abstract

Carcinogenesis is a complicated process and originates from genetic, epigenetic, and environmental factors. Recent studies have reported a potential critical role for the fat mass and obesity-associated (FTO) gene in carcinogenesis through different signaling pathways such as mRNA N6-methyladenosine (m6A) demethylation. The most common internal modification in mammalian mRNA is the m6A RNA methylation that has significant biological functioning through regulation of cancer-related cellular processes. Some environmental factors, like physical activity and dietary intake, may influence signaling pathways engaged in carcinogenesis, through regulating FTO gene expression. In addition, people with FTO gene polymorphisms may be differently influenced by cancer risk factors, for example, FTO risk allele carriers may need a higher intake of nutrients to prevent cancer than others. In order to obtain a deeper viewpoint of the FTO, lifestyle, and cancer-related pathway interactions, this review aims to discuss upstream and downstream pathways associated with the FTO gene and cancer. The present study discusses the possible mechanisms of interaction of the FTO gene with various cancers and provides a comprehensive picture of the lifestyle factors affecting the FTO gene as well as the possible downstream pathways that lead to the effect of the FTO gene on cancer.