FH and cancer: Mutations in FH lead to reduced enzyme activity and accumulation of fumarate, further causing dysfunction of mitochondrial respiratory chain activity.[3] Furthermore, accumulated fumarate could improve the expression of hypoxia-inducible factor 1α and nuclear factor (erythroid-2) like-2 transcription factor, which participate in various pathophysiological processes such as angiogenesis, epithelial-to-mesenchymal transition, and cancer progression.[4] Furthermore, FH has also been recognized as a suppressor of homologous recombination DNA repair, thus compromising genome integrity.[5]