The Role of Inherited TPMT and COMT Genetic Variation in Cisplatin-Induced Ototoxicity in Children With Cancer

被引：70

作者：

Yang, J. J. ^{[1
]}

Lim, J. Y. S. ^{[1
,2
]}

Huang, J. ^{[3
]}

Bass, J. ^{[4
]}

Wu, J. ^{[3
]}

Wang, C. ^{[3
]}

Fang, J. ^{[5
]}

Stewart, E. ^{[6
]}

Harstead, E. H. ^{[1
]}

Robinson, G. W. ^{[6
]}

Evans, W. E. ^{[1
]}

Pappo, A. ^{[6
]}

Zuo, J. ^{[5
]}

Relling, M. V. ^{[1
]}

Onar-Thomas, A. ^{[3
]}

Gajjar, A. ^{[6
]}

Stewart, C. F. ^{[1
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pediat, Singapore 117595, Singapore

[3] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA

[4] St Jude Childrens Res Hosp, Dept Pediat Med, Memphis, TN 38105 USA

[5] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA

[6] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2013年 / 94卷 / 02期

基金：

美国国家卫生研究院;

关键词：

THIOPURINE S-METHYLTRANSFERASE; HEARING-LOSS; RECEIVING CISPLATIN; MERCAPTOPURINE; IDENTIFICATION; CHEMOTHERAPY; RADIOTHERAPY; CONSENSUS; VARIANTS;

D O I：

10.1038/clpt.2013.121

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：252 / 259

页数：8

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