Genetic predisposition and treatment-related leukemia.
Treatment-related leukemias are one of the most devastating late complications of cancer therapy. Patients with rare cancer predisposition syndromes including neurofibromatosis type 1 and inherited p53 mutations are at an increased risk for this complication. Other patients may have increased susceptibility because they possess common genetic polymorphisms in drug-metabolizing enzymes that result in impaired detoxification of chemotherapy or inefficient repair of drug-induced genetic damage. We review studies that have identified a potential role for polymorphisms in the genes encoding the glutathione-S-transferases (GSTs), NAD(P) H: quinone oxidoreductase, myeloperoxidase, N-acetyltransferase (NATs), cytochrome P450 (CYP) 1A1 and 3A4, methylenetetrahydrofolate reductase (MTHFR), cystathionine-beta-synthase (CBS), and others in the etiology of primary or secondary acute leukemias, and therapy-related complications. The identification of high risk polymorphisms and use of pharmacogenetically-guided therapies holds promise to improve the outcome of cancer therapy and reduce the risk of treatment-related leukemias.
Perentesis
J P
JP
Division of Pediatric Hematology, Oncology, and Blood & Marrow Transplant, University of Minnesota Cancer Center, Minneapolis, Minnesota, USA. peren001@umn.edu
D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007938:Leukemia / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic
D005982:Glutathione Transferase