TY - JOUR
T1 - The role of inherited TPMT and COMT genetic variation in cisplatin-induced ototoxicity in children with cancer
AU - Yang, J. J.
AU - Lim, J. Y.S.
AU - Huang, J.
AU - Bass, J.
AU - Wu, J.
AU - Wang, C.
AU - Fang, J.
AU - Stewart, E.
AU - Harstead, E. H.
AU - E.s.,
AU - Robinson, G. W.
AU - Evans, W. E.
AU - Pappo, A.
AU - Zuo, J.
AU - Relling, M. V.
AU - Onar-Thomas, A.
AU - Gajjar, A.
AU - Stewart, C. F.
PY - 2013/8
Y1 - 2013/8
N2 - Ototoxicity is a debilitating side effect of platinating agents with substantial interpatient variability. We sought to evaluate the association of thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) genetic variations with cisplatin-related hearing damage in the context of frontline pediatric cancer treatment protocols. In 213 children from the St. Jude Medulloblastoma-96 and-03 protocols, hearing loss was related to younger age (P = 0.013) and craniospinal irradiation (P = 0.001), but did not differ by TPMT or COMT variants. Results were similar in an independent cohort of 41 children from solid-tumor frontline protocols. Functional hearing loss or hair cell damage was not different in TPMT knockout vs. wild-type mice following cisplatin treatment, and neither TPMT nor COMT variant was associated with cisplatin cytotoxicity in lymphoblastoid cell lines. In conclusion, our results indicated that TPMT or COMT genetic variation was not related to cisplatin ototoxicity in children with cancer and did not influence cisplatin-induced hearing damage in laboratory models.
AB - Ototoxicity is a debilitating side effect of platinating agents with substantial interpatient variability. We sought to evaluate the association of thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) genetic variations with cisplatin-related hearing damage in the context of frontline pediatric cancer treatment protocols. In 213 children from the St. Jude Medulloblastoma-96 and-03 protocols, hearing loss was related to younger age (P = 0.013) and craniospinal irradiation (P = 0.001), but did not differ by TPMT or COMT variants. Results were similar in an independent cohort of 41 children from solid-tumor frontline protocols. Functional hearing loss or hair cell damage was not different in TPMT knockout vs. wild-type mice following cisplatin treatment, and neither TPMT nor COMT variant was associated with cisplatin cytotoxicity in lymphoblastoid cell lines. In conclusion, our results indicated that TPMT or COMT genetic variation was not related to cisplatin ototoxicity in children with cancer and did not influence cisplatin-induced hearing damage in laboratory models.
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U2 - 10.1038/clpt.2013.121
DO - 10.1038/clpt.2013.121
M3 - Article
C2 - 23820299
AN - SCOPUS:84880753477
SN - 0009-9236
VL - 94
SP - 252
EP - 259
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 2
ER -
