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

Nat Genet. 2015 Mar;47(3):263-6. doi: 10.1038/ng.3217. Epub 2015 Feb 9.

Authors

Heng Xu¹, Giles W Robinson², Jie Huang³, Joshua Yew-Suang Lim⁴, Hui Zhang⁵, Johnnie K Bass⁶, Alberto Broniscer², Murali Chintagumpala⁷, Ute Bartels⁸, Sri Gururangan⁹, Tim Hassall¹⁰, Michael Fisher¹¹, Richard Cohn¹², Tetsuji Yamashita¹³, Tal Teitz¹³, Jian Zuo¹³, Arzu Onar-Thomas³, Amar Gajjar², Clinton F Stewart⁵, Jun J Yang⁵

Affiliations

¹ 1] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Laboratory Medicine, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
² Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
³ Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
⁴ 1] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁵ Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
⁶ Rehabilitation Services, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
⁷ Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
⁸ Department of Haematology and Oncology, Hospital for Sick Children, Toronto, Ontario, Canada.
⁹ Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
¹⁰ Department of Oncology, The Royal Children's Hospital, Parkville, Victoria, Australia.
¹¹ Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹² School of Women's and Children's Health, University of New South Wales, Kensington, New South Wales, Australia.
¹³ Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

PMID: 25665007
PMCID: PMC4358157
DOI: 10.1038/ng.3217

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.

Trial registration: ClinicalTrials.gov NCT00033211 NCT00085202.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acid Anhydride Hydrolases / genetics*
Acylphosphatase
Antineoplastic Agents / adverse effects*
Brain Neoplasms / drug therapy
Brain Neoplasms / enzymology
Brain Neoplasms / genetics
Child, Preschool
Cisplatin / adverse effects*
Clinical Trials as Topic
Female
Genetic Predisposition to Disease
Genome-Wide Association Study / methods
Hearing Loss / chemically induced*
Hearing Loss / enzymology
Hearing Loss / genetics*
Humans
Infant
Male
Polymorphism, Single Nucleotide

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

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