Pharmacogenomics of cisplatin-induced neurotoxicities: Hearing loss, tinnitus, and peripheral sensory neuropathy.
Antineoplastic Agents
/ adverse effects
Cisplatin
/ therapeutic use
Genome-Wide Association Study
Hearing Loss
/ chemically induced
Humans
Male
Neurotoxicity Syndromes
Peripheral Nervous System Diseases
/ chemically induced
Pharmacogenetics
Sensation Disorders
Testicular Neoplasms
/ genetics
Tinnitus
/ chemically induced
GWAS
cisplatin
neurotoxicity
ototoxicity
survivorship
testicular cancer
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
revised:
14
01
2022
received:
02
12
2021
accepted:
19
01
2022
pubmed:
25
3
2022
medline:
26
7
2022
entrez:
24
3
2022
Statut:
ppublish
Résumé
Cisplatin is a critical component of first-line chemotherapy for several cancers, but causes peripheral sensory neuropathy, hearing loss, and tinnitus. We aimed to identify comorbidities for cisplatin-induced neurotoxicities among large numbers of similarly treated patients without the confounding effect of cranial radiotherapy. Utilizing linear and logistic regression analyses on 1680 well-characterized cisplatin-treated testicular cancer survivors, we analyzed associations of hearing loss, tinnitus, and peripheral neuropathy with nongenetic comorbidities. Genome-wide association studies and gene-based analyses were performed on each phenotype. Hearing loss, tinnitus, and peripheral neuropathy, accounting for age and cisplatin dose, were interdependent. Survivors with these neurotoxicities experienced more hypertension and poorer self-reported health. In addition, hearing loss was positively associated with BMIs at clinical evaluation and nonwork-related noise exposure (>5 h/week). Tinnitus was positively associated with tobacco use, hypercholesterolemia, and noise exposure. We observed positive associations between peripheral neuropathy and persistent vertigo, tobacco use, and excess alcohol consumption. Hearing loss and TXNRD1, which plays a key role in redox regulation, showed borderline significance (p = 4.2 × 10 Genetics variants in TXNRD1 and WNT8A are notable risk factors for hearing loss and tinnitus, respectively. Future studies should investigate these genes and if replicated, identify their potential impact on preventive strategies.
Identifiants
pubmed: 35322580
doi: 10.1002/cam4.4644
pmc: PMC9302309
doi:
Substances chimiques
Antineoplastic Agents
0
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2801-2816Subventions
Organisme : NCI NIH HHS
ID : R01 CA157823
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Références
CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
pubmed: 21296855
J Neurol Neurosurg Psychiatry. 2007 Feb;78(2):114-22
pubmed: 17229743
Mech Dev. 2013 Feb;130(2-3):160-8
pubmed: 23041177
Neuro Oncol. 2012 Sep;14 Suppl 4:iv45-54
pubmed: 23095830
Ann Oncol. 2017 Nov 01;28(11):2670-2679
pubmed: 29045502
Int Tinnitus J. 2007;13(2):143-9
pubmed: 18229794
J Clin Oncol. 2014 Oct 1;32(28):3085-92
pubmed: 25024068
BMC Cancer. 2020 Apr 6;20(1):284
pubmed: 32252689
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219
pubmed: 25885710
Nat Genet. 2016 Oct;48(10):1279-83
pubmed: 27548312
Nature. 2012 Mar 28;483(7391):603-7
pubmed: 22460905
Clin Cancer Res. 2019 Jul 1;25(13):4104-4116
pubmed: 30952644
Nat Genet. 2016 Oct;48(10):1284-1287
pubmed: 27571263
Acta Otolaryngol. 2009 Sep;129(9):929-34
pubmed: 19153847
J Hematol Oncol. 2017 May 5;10(1):101
pubmed: 28476164
J Clin Oncol. 2018 May 20;36(15):1505-1512
pubmed: 29617189
Blood Press. 2015;24(4):199-205
pubmed: 26032520
Clin Cancer Res. 2020 Dec 15;26(24):6550-6558
pubmed: 32998964
Med Res Rev. 2004 Jan;24(1):40-89
pubmed: 14595672
Ann Oncol. 2013 Feb;24(2):454-462
pubmed: 22910842
Clin Cancer Res. 2018 Apr 15;24(8):1866-1871
pubmed: 29358504
Cancer Res. 2021 Nov 1;81(21):5369-5376
pubmed: 34380632
Nat Commun. 2017 Nov 28;8(1):1826
pubmed: 29184056
Brain. 2007 Apr;130(Pt 4):1076-88
pubmed: 17301082
Eur J Cancer. 2002 Feb;38(3):387-91
pubmed: 11818204
Cancer. 2014 Jun 15;120(12):1890-7
pubmed: 24619793
Circulation. 2001 Jan 2;103(1):113-8
pubmed: 11136695
J Natl Cancer Inst. 2014 Mar 12;106(5):
pubmed: 24623533
Cancer Med. 2022 Jul;11(14):2801-2816
pubmed: 35322580
Nucleic Acids Res. 2013 Jan;41(Database issue):D955-61
pubmed: 23180760
Clin Cancer Res. 2019 Feb 15;25(4):1147-1155
pubmed: 30305294
Clin Cancer Res. 2017 Jul 1;23(13):3325-3333
pubmed: 28039263
Qual Life Res. 2006 Jun;15(5):791-800
pubmed: 16721639
J Clin Oncol. 2016 Aug 10;34(23):2712-20
pubmed: 27354478
Int J Oncol. 2001 Jul;19(1):123-7
pubmed: 11408932
Int J Oncol. 2005 Apr;26(4):1129-33
pubmed: 15754011
Indian J Otolaryngol Head Neck Surg. 2013 Dec;65(Suppl 3):614-8
pubmed: 24427724
Nat Methods. 2021 Aug;18(8):843-844
pubmed: 34172972
Nat Genet. 2016 Nov;48(11):1443-1448
pubmed: 27694958
Lancet. 2013 Nov 9;382(9904):1600-7
pubmed: 23827090
J Natl Cancer Inst. 2009 Dec 16;101(24):1682-95
pubmed: 19940282
PLoS One. 2014 Feb 28;9(2):e90279
pubmed: 24587312
JAMA Netw Open. 2019 Apr 5;2(4):e191703
pubmed: 30951159
Clin Cancer Res. 2017 Oct 1;23(19):5757-5768
pubmed: 28611204
Front Neurol. 2016 Oct 05;7:171
pubmed: 27761128
J Nutr. 2011 Jul;141(7):1355-61
pubmed: 21613455
Cancer Treat Rev. 2007 Feb;33(1):9-23
pubmed: 17084534
Sci Rep. 2019 Mar 5;9(1):3455
pubmed: 30837596
Elife. 2018 Jul 31;7:
pubmed: 30060804