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.
authors: 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.
authors: Heng
authors: H
authors: Xu
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Giles W
authors: GW
authors: Robinson
authors: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Jie
authors: J
authors: Huang
authors: 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.
authors: Joshua Yew-Suang
authors: JY
authors: Lim
authors: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Hui
authors: H
authors: Zhang
authors: Rehabilitation Services, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Johnnie K
authors: JK
authors: Bass
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Alberto
authors: A
authors: Broniscer
authors: Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
authors: Murali
authors: M
authors: Chintagumpala
authors: Department of Haematology and Oncology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Ute
authors: U
authors: Bartels
authors: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
authors: Sri
authors: S
authors: Gururangan
authors: Department of Oncology, The Royal Children's Hospital, Parkville, Victoria, Australia.
authors: Tim
authors: T
authors: Hassall
authors: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors: Michael
authors: M
authors: Fisher
authors: School of Women's and Children's Health, University of New South Wales, Kensington, New South Wales, Australia.
authors: Richard
authors: R
authors: Cohn
authors: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Tetsuji
authors: T
authors: Yamashita
authors: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Tal
authors: T
authors: Teitz
authors: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Jian
authors: J
authors: Zuo
authors: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Arzu
authors: A
authors: Onar-Thomas
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Amar
authors: A
authors: Gajjar
authors: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Clinton F
authors: CF
authors: Stewart
authors: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Jun J
authors: JJ
authors: Yang
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D034381:Hearing Loss / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D000097024:Acylphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D000970:Antineoplastic Agents; D002945:Cisplatin; D000097024:Acylphosphatase