Conflict of interest: Nothing to declare.
Glutathione S-transferase P1 single nucleotide polymorphism predicts permanent ototoxicity in children with medulloblastoma†
Article first published online: 12 OCT 2012
Copyright © 2012 Wiley Periodicals, Inc.
Pediatric Blood & Cancer
Volume 60, Issue 4, pages 593–598, April 2013
How to Cite
Rednam, S., Scheurer, M. E., Adesina, A., Lau, C. C. and Okcu, M. F. (2013), Glutathione S-transferase P1 single nucleotide polymorphism predicts permanent ototoxicity in children with medulloblastoma. Pediatr. Blood Cancer, 60: 593–598. doi: 10.1002/pbc.24366
- Issue published online: 13 FEB 2013
- Article first published online: 12 OCT 2012
- Manuscript Accepted: 17 SEP 2012
- Manuscript Received: 6 JUN 2012
- National Institutes of Health. Grant Number: P50CA127001-04
- Gillson Longenbaugh Foundation
- John S. Dunn Research Foundation
- Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation
- American Brain Tumor Association
- glutathione S-transferase;
Glutathione S-transferase (GST) enzymes are involved in detoxifying chemotherapy and clearing reactive oxygen species formed by radiation. We explored the relationship between the host GSTP1 105 A > G polymorphism (rs1695), tumor GSTpi protein expression, and clinical outcomes in pediatric medulloblastoma. We hypothesized that the GSTP1 105 G-allele and increased tumor GSTpi expression would be associated with lower progression-free survival and fewer adverse events.
The study included 106 medulloblastoma/primitive neuroectodermal tumor (PNET) patients seen at Texas Children's Cancer Center. Genotyping was performed using an Illumina HumanOmni1-Quad BeadChip and GSTpi expression was assessed using immunohistochemistry. We used the Kaplan–Meier method for survival analyses and logistic regression for toxicity comparisons.
Patients with a GSTP1 105 AG/GG genotype (vs. AA) or who had received high dose craniospinal radiation (≥34 Gy vs. <26 Gy) had a greater risk of requiring hearing aids than their counterparts (OR 4.0, 95% CI 1.2–13.6, and OR 3.1, 95% CI 1.1–8.8, respectively, n = 69). Additionally, there was a statistically significant interaction between these variables. Compared with the lowest risk group (GSTP1 105 AA–low dose radiation), patients with a GSTP1 105 AG/GG genotype who received high dose radiation were 8.4 times more likely to require hearing aids (95% CI 1.4–49.9, p-trend = 0.005, n = 69). When adjusted for age, cumulative cisplatin dose, and amifostine use, the association remained.
The GSTP1 105 G-allele is associated with permanent ototoxicity in pediatric medulloblastoma/PNET and strongly interacts with radiation dose. Patients with this allele should be considered for clinical trials employing radiation dose modifications and cytoprotectant strategies. Pediatr Blood Cancer 2013; 60: 593–598. © 2012 Wiley Periodicals, Inc.