OBJECTIVE: Irreversible hearing loss is a frequent side effect of the chemotherapeutic agent cisplatin and shows considerable interpatient variability. The variant rs1872328 in the ACYP2 gene was recently identified as a risk factor for the development of cisplatin-induced ototoxicity in children with brain tumors. We aimed to replicate this finding in patients with osteosarcoma. METHODS: An independent cohort of 156 patients was genotyped for the rs1872328 variant and evaluated for the presence of cisplatin-induced ototoxicity. RESULTS: A significant association was observed between carriership of the A allele and cisplatin-induced ototoxicity after the end of treatment (P=0.027). CONCLUSION: This is the first study replicating the association of ACYP2 variant rs1872328 with cisplatin-induced ototoxicity in patients with osteosarcoma who did not receive potentially ototoxic cranial irradiation. Hence, the ACYP2 variant should be considered a predictive pharmacogenetic marker for hearing loss, which may be used to guide therapies for patients treated with cisplatin.
OBJECTIVE: Irreversible hearing loss is a frequent side effect of the chemotherapeutic agent cisplatin and shows considerable interpatient variability. The variant rs1872328 in the ACYP2 gene was recently identified as a risk factor for the development of cisplatin-induced ototoxicity in children with brain tumors. We aimed to replicate this finding in patients with osteosarcoma. METHODS: An independent cohort of 156 patients was genotyped for the rs1872328 variant and evaluated for the presence of cisplatin-induced ototoxicity. RESULTS: A significant association was observed between carriership of the A allele and cisplatin-induced ototoxicity after the end of treatment (P=0.027). CONCLUSION: This is the first study replicating the association of ACYP2 variant rs1872328 with cisplatin-induced ototoxicity in patients with osteosarcoma who did not receive potentially ototoxic cranial irradiation. Hence, the ACYP2 variant should be considered a predictive pharmacogenetic marker for hearing loss, which may be used to guide therapies for patients treated with cisplatin.
Authors: Heather E Wheeler; Eric R Gamazon; Robert D Frisina; Carlos Perez-Cervantes; Omar El Charif; Brandon Mapes; Sophie D Fossa; Darren R Feldman; Robert J Hamilton; David J Vaughn; Clair J Beard; Chunkit Fung; Christian Kollmannsberger; Jeri Kim; Taisei Mushiroda; Michiaki Kubo; Shirin Ardeshir-Rouhani-Fard; Lawrence H Einhorn; Nancy J Cox; M Eileen Dolan; Lois B Travis Journal: Clin Cancer Res Date: 2016-12-30 Impact factor: 12.531
Authors: Matthew R Trendowski; Omar El Charif; Paul C Dinh; Lois B Travis; M Eileen Dolan Journal: Clin Cancer Res Date: 2018-10-10 Impact factor: 12.531
Authors: Daniel B Hawcutt; Munir Pirmohamed; Signe Thiesen; Peng Yin; Andrea L Jorgensen; Jieying Eunice Zhang; Valentina Manzo; Laurence McEvoy; Christopher Barton; Susan Picton; Simon Bailey; Penelope Brock; Harish Vyas; David Walker; Guy Makin; Srinivas Bandi; Barry Pizer Journal: Pharmacogenet Genomics Date: 2017-06 Impact factor: 2.089
Authors: Evangelia Tserga; Tara Nandwani; Niklas K Edvall; Jan Bulla; Poulam Patel; Barbara Canlon; Christopher R Cederroth; David M Baguley Journal: Sci Rep Date: 2019-03-05 Impact factor: 4.379