[One perspective of the genetic correlations between obesity, type 2 diabetes and cancer]

Obesity, type 2 diabetes, cardiovascular diseases and malignancies are nowadays the most significant demographic disorders that dominate the statistics of mortality. There is evidence suggesting metabolic and molecular genetic correlations behind their similar epidemiological behaviour. The latter can be recognised on the level of shared cell surface receptors, intracellular signalling pathways and genes. By 2006, the entire human genome has been successfully mapped. This was followed by a growing number of genome-wide association studies, which have brought breakthroughs in the understanding of genetic background of a variety of diseases characterized by polygenic inheritance that do not follow the Mendelian constraints. They have made it possible to pinpoint specific gene variants and loci that are simultaneously linked to the risk of multiple diseases. Hundreds of novel genes underlying polygenic obesity and type 2 diabetes have been uncovered, some of which are thought to have a role in cancer. The complex significance of the best understood FTO and TCF7L2 genes was one of the first to be considered. Their polymorphisms affect the clinical manifestations of both obesity and diabetes. FTO may have a direct impact on the etiology of the former disorder and TCF7L2 on the latter, while both genes may have an indirect effect on the other disease’s phenotype. According to literature data, the FTO enzyme protein may be implicated in oncogenesis through post-transcriptional regulation of gene expression and through modulation of mTOR, and that the TCF7L2 gene product is known to be a transcription factor that may promote malignant tumour development by manipulating biological pathways. It can therefore be reasonably inferred that the investigation of the FTO and TCF7L2 genes may be of importance for diagnosis, management and prognostication of all three epidemics, namely, obesity, type 2 diabetes and malignant neoplasms. Conclusively it can be argued that a thorough assessment of the newer gene polymorphisms and their relations, revealed by gene association studies, is of shared future interest for the medical professionals involved in oncodiabetologic patient care and for the affected individuals. Orv Hetil. 2024; 165(13): 499–509.