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High-Throughput Detection of Glutathione S-Transferase Polymorphic Alleles in a Pediatric Cancer Population

¹ Division of Pediatric Hematology-Oncology, Department of Pediatrics, ² Genomics Core Facility, and ³ Biomedical Statistics, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, and ⁴ Section of Molecular Therapeutics, Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas

Polymorphisms of glutathione S-transferase (GST) enzymes have been correlated with altered risk of several cancers, as well as altered response and toxicity from cancer chemotherapy. We report a low cost, highly reproducible and specific PCR-based high-throughput assay for genotyping different GSTs designed for use in large clinical trials. In comparison to an alternative genotyping method (single nucleotide extension), the sensitivity and specificity of the high throughput assay was shown to be 92 and 97%, respectively, depending on the source of genomic DNA. Using the high-throughput assay, we demonstrate by multivariate analysis an increased risk of acute lymphoblastic leukemia, glial brain tumors, and osteosarcoma for patients carrying nonnull alleles of GSTM1 and/or GSTT1.