fumarate hydratase and cancer – pro
The FH gene provides instructions for making an enzyme called fumarase (also known as fumarate hydratase). FH gene mutations may interfere with the enzyme’s role in the citric acid cycle, resulting in a buildup of fumarate. Researchers believe that the excess fumarate may interfere with the regulation of oxygen levels in the cell. Chronic oxygen deficiency (hypoxia) in cells with two mutated copies of the FH gene may encourage tumor formation and result in the tendency to develop leiomyomas and renal cell cancer.
A number of families with this mutation have been reported but there are no guidelines as to surveillance. A recent report of one case recommended annual surveillance. What modality should be used is not clear. Therefore, there is not sufficient credible evidence to recommend biannual MRI screening.
Gardie, B., Remenieras, A., Kattygnarath, D., Bombled, J., Lefevre, S., Perrier-Trudova, V., Rustin, P., Barrois, M., Slama, A., Avril, M.-F., Bessis, D., Caron, O., and 41 others. Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma. J. Med. Genet. 48: 226-234, 2011. Note: Erratum: J. Med. Genet. 48: 576 only, 2011.
Obstet Gynecol. 2015 Jul;126(1):90-2.
Mann ML1, Ezzati M, Tarnawa ED, Carr BR.Fumarate Hydratase Mutation in a Young Woman With Uterine Leiomyomas and a Family History of Renal Cell Cancer.Obstet Gynecol. 2015 Jul;126(1):90-2.