Increased risk for aplastic anemia and myelodysplastic syndrome in individuals lacking glutathione S-transferase genes

• Published in: Pediatric Blood & Cancer 2004-02, Vol.42 (2), p.122-126
• Main Authors: Sutton, Joanne F., Stacey, Michael, Kearns, William G., Rieg, Thomas S., Young, Neal S., Liu, Johnson M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Aplastic - diagnosis; Anemia, Aplastic - etiology; Anemia, Aplastic - genetics; aplastic anemia; Biological and medical sciences; Bone Marrow - pathology; Child; Child, Preschool; chromosomal abnormality; Chromosome Aberrations; Chromosomes, Human, Pair 7 - genetics; Chromosomes, Human, Pair 8 - genetics; DNA, Neoplasm - genetics; Female; General aspects; Genotype; glutathione S-transferase; Glutathione Transferase - deficiency; Glutathione Transferase - genetics; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Male; Medical sciences; Middle Aged; myelodysplastic syndrome; Myelodysplastic Syndromes - diagnosis; Myelodysplastic Syndromes - etiology; Myelodysplastic Syndromes - genetics; Risk Factors; Tumors
• ISSN: 1545-5009; 1545-5017; 1096-911X
• DOI: 10.1002/pbc.10479

Background Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are marrow failure states that may be associated with chromosomal instability. An absence of the glutathione S‐transferase (GST) enzyme may genetically predispose individuals to AA or MDS. Procedure and Results To test this hypothesis, we determined the GSTM1 and GSTT1 genotypes in a total of 196 patients using multiplex PCR. The GSTT1 null genotype was found to be overrepresented in Caucasian, Asian, and Hispanic patients with either AA or MDS. We confirmed a difference in the expected frequency of the GSTM1 null genotype in Caucasian MDS patients. The double null GSTM1/GSTT1 genotype was also overrepresented in Caucasian AA and MDS patients. In our population, 26% of AA patients and 40% of MDS patients had a chromosomal abnormality identified by karyotype or FISH analyses for chromosomes 7 and 8. Patients with AA and the GSTT1 null genotype had an increased frequency of chromosomal abnormalities (P = 0.003). Conclusion There seems to be an increased risk for AA and MDS in individuals lacking GSTT1 or both GSTM1/GSTT1. Published 2003 Wiley‐Liss, Inc.