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. Med. Pediatr. Oncol. 36:541–548, 2001. © 2001 Wiley‐Liss, Inc.