Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss

Heng Xu; Giles W. Robinson; Jie Huang; Joshua Yew Suang Lim; Hui Zhang; Johnnie K. Bass; Alberto Broniscer; Murali Chintagumpala; Ute Bartels; Sri Gururangan; Tim Hassall; Michael Fisher; Richard Cohn; Tetsuji Yamashita; Tal Teitz; Jian Zuo; Arzu Onar-Thomas; Amar Gajjar; Clinton F. Stewart; Jun J. Yang

doi:10.1038/ng.3217

Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss

Heng Xu, Giles W. Robinson, Jie Huang, Joshua Yew Suang Lim, Hui Zhang, Johnnie K. Bass, Alberto Broniscer, Murali Chintagumpala, Ute Bartels, Sri Gururangan, Tim Hassall, Michael Fisher, Richard Cohn, Tetsuji Yamashita, Tal Teitz, Jian Zuo, Arzu Onar-Thomas, Amar Gajjar, Clinton F. Stewart, Jun J. Yang^*

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

90 Scopus citations

Abstract

Taking a genome-wide association study approach, we identified inherited genetic variations in ACYP2 associated with cisplatin-related ototoxicity (rs1872328: P = 3.9 × 10 -8, hazard ratio = 4.5) in 238 children with newly diagnosed brain tumors, with independent replication in 68 similarly treated children. The ACYP2 risk variant strongly predisposed these patients to precipitous hearing loss and was related to ototoxicity severity. These results point to new biology underlying the ototoxic effects of platinum agents.

Original language	English (US)
Pages (from-to)	263-266
Number of pages	4
Journal	Nature Genetics
Volume	47
Issue number	3
DOIs	https://doi.org/10.1038/ng.3217
State	Published - Feb 25 2015

ASJC Scopus subject areas

Genetics

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Xu, H., Robinson, G. W., Huang, J., Lim, J. Y. S., Zhang, H., Bass, J. K., Broniscer, A., Chintagumpala, M., Bartels, U., Gururangan, S., Hassall, T., Fisher, M., Cohn, R., Yamashita, T., Teitz, T., Zuo, J., Onar-Thomas, A., Gajjar, A., Stewart, C. F., & Yang, J. J. (2015). Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss. Nature Genetics, 47(3), 263-266. https://doi.org/10.1038/ng.3217

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title = "Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss",

abstract = "Taking a genome-wide association study approach, we identified inherited genetic variations in ACYP2 associated with cisplatin-related ototoxicity (rs1872328: P = 3.9 × 10 -8, hazard ratio = 4.5) in 238 children with newly diagnosed brain tumors, with independent replication in 68 similarly treated children. The ACYP2 risk variant strongly predisposed these patients to precipitous hearing loss and was related to ototoxicity severity. These results point to new biology underlying the ototoxic effects of platinum agents.",

author = "Heng Xu and Robinson, {Giles W.} and Jie Huang and Lim, {Joshua Yew Suang} and Hui Zhang and Bass, {Johnnie K.} and Alberto Broniscer and Murali Chintagumpala and Ute Bartels and Sri Gururangan and Tim Hassall and Michael Fisher and Richard Cohn and Tetsuji Yamashita and Tal Teitz and Jian Zuo and Arzu Onar-Thomas and Amar Gajjar and Stewart, {Clinton F.} and Yang, {Jun J.}",

note = "Funding Information: In the version of this article initially published, the authors neglected to acknowledge that the work was also supported by US National Institutes of Health grant R01 CA154619. The error has been corrected in the HTML and PDF versions of the article. Funding Information: We thank S. Throm for coordinating patient samples, S. Hughes for curating the ototoxicity data, all patients and their parents who participated in the St. Jude protocols included in this study, G. Koh (National University of Singapore) for her assistance in genome-wide genotyping, and L. Robison and K. Ness (St. Jude Children{\textquoteright}s Research Hospital) for insightful discussions. This work was supported by the US National Institutes of Health (P30 CA21765-34, U01 GM92666 and R01 CA154619) and the American Lebanese Syrian Associated Charities (ALSAC).",

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Xu, H, Robinson, GW, Huang, J, Lim, JYS, Zhang, H, Bass, JK, Broniscer, A, Chintagumpala, M, Bartels, U, Gururangan, S, Hassall, T, Fisher, M, Cohn, R, Yamashita, T, Teitz, T, Zuo, J, Onar-Thomas, A, Gajjar, A, Stewart, CF & Yang, JJ 2015, 'Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss', Nature Genetics, vol. 47, no. 3, pp. 263-266. https://doi.org/10.1038/ng.3217

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AU - Robinson, Giles W.

AU - Huang, Jie

AU - Lim, Joshua Yew Suang

AU - Zhang, Hui

AU - Bass, Johnnie K.

AU - Broniscer, Alberto

AU - Chintagumpala, Murali

AU - Bartels, Ute

AU - Gururangan, Sri

AU - Hassall, Tim

AU - Fisher, Michael

AU - Cohn, Richard

AU - Yamashita, Tetsuji

AU - Teitz, Tal

AU - Zuo, Jian

AU - Onar-Thomas, Arzu

AU - Gajjar, Amar

AU - Stewart, Clinton F.

AU - Yang, Jun J.

N1 - Funding Information: In the version of this article initially published, the authors neglected to acknowledge that the work was also supported by US National Institutes of Health grant R01 CA154619. The error has been corrected in the HTML and PDF versions of the article. Funding Information: We thank S. Throm for coordinating patient samples, S. Hughes for curating the ototoxicity data, all patients and their parents who participated in the St. Jude protocols included in this study, G. Koh (National University of Singapore) for her assistance in genome-wide genotyping, and L. Robison and K. Ness (St. Jude Children’s Research Hospital) for insightful discussions. This work was supported by the US National Institutes of Health (P30 CA21765-34, U01 GM92666 and R01 CA154619) and the American Lebanese Syrian Associated Charities (ALSAC).

PY - 2015/2/25

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AB - Taking a genome-wide association study approach, we identified inherited genetic variations in ACYP2 associated with cisplatin-related ototoxicity (rs1872328: P = 3.9 × 10 -8, hazard ratio = 4.5) in 238 children with newly diagnosed brain tumors, with independent replication in 68 similarly treated children. The ACYP2 risk variant strongly predisposed these patients to precipitous hearing loss and was related to ototoxicity severity. These results point to new biology underlying the ototoxic effects of platinum agents.

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Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss

Abstract

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