The genetic vulnerability to cisplatin ototoxicity: a systematic review.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Genetic Predisposition to Disease* ; Pharmacogenomic Variants*; Antineoplastic Agents/*adverse effects ; Cisplatin/*adverse effects ; Ototoxicity/*etiology; Alleles ; Antineoplastic Agents/therapeutic use ; Cisplatin/therapeutic use ; Genome-Wide Association Study ; Humans ; Odds Ratio ; Polymorphism, Single Nucleotide ; Publication Bias

Ototoxicity is one of the major side-effects of platinum-based chemotherapy, in particular cisplatin (cis-diammine dichloroplatinum II). To our knowledge, no systematic review has previously provided a quantitative summary estimate of the impact of genetics upon the risk of developing hearing loss. We searched Embase, Medline, ASSIA, Pubmed, Scopus, and Web of Science, for studies documenting the genetic risk of ototoxicity in patients with cancer treated with cisplatin. Titles/abstracts and full texts were reviewed for inclusion. Meta-analytic estimates of risk (Odds Ratio) from the pooled data were calculated for studies that have been repeated twice or more. The search identified 3891 papers, of which 30 were included. The majority were retrospective (44%), ranging from n = 39 to n = 317, some including only patients younger than 25 years of age (33%), and some on both genders (80%). The most common cancers involved were osteosarcoma (53%), neuroblastoma (37%), prostate (17%) and reproductive (10%). Most studies performed genotyping, though only 5 studies performed genome-wide association studies. Nineteen single-nucleotide polymorphisms (SNPs) from 15 genes were repeated more than twice. Meta-analysis of group data indicated that rs1872328 on ACYP2, which plays a role in calcium homeostasis, increases the risk of ototoxicity by 4.61 (95% CI: 3.04-7.02; N = 696, p < 0.0001) as well as LRP2 rs4668123 shows a cumulated Odds Ratio of 3.53 (95% CI: 1.48-8.45; N = 118, p = 0.0059), which could not be evidenced in individual studies. Despite the evidence of heterogeneity across studies, these meta-analytic results from 30 studies are consistent with a view of a genetic predisposition to platinum-based chemotherapy mediated ototoxicity. These new findings are informative and encourage the genetic screening of cancer patients in order to identify patients with greater vulnerability of developing hearing loss, a condition having a potentially large impact on quality of life. More studies are needed, with larger sample size, in order to identify additional markers of ototoxic risk associated with platinum-based chemotherapy and investigate polygenic risks, where multiple markers may exacerbate the side-effects.

Laryngoscope. 2006 Jan;116(1):72-4. (PMID: 16481813)
PLoS One. 2017 Apr 13;12(4):e0175711. (PMID: 28406961)
Clin Pharmacol Ther. 2013 Aug;94(2):243-51. (PMID: 23588304)
JAMA Oncol. 2017 Nov 1;3(11):1558-1562. (PMID: 28448657)
Nat Commun. 2017 Nov 21;8(1):1654. (PMID: 29162831)
Kidney Int. 2007 Oct;72(8):931-5. (PMID: 17653135)
Oncogene. 2003 Oct 20;22(47):7265-79. (PMID: 14576837)
J Clin Oncol. 2018 Jan 1;36(1):94-95. (PMID: 29016229)
Neurotoxicology. 2017 May;60:1-9. (PMID: 28223157)
Oncotarget. 2018 Apr 24;9(31):21696-21714. (PMID: 29774096)
Int J Toxicol. 2018 May/Jun;37(3):195-206. (PMID: 29575954)
Int J Audiol. 2018 Sep;57(sup4):S89-S98. (PMID: 29276851)
Gene. 2016 Nov 30;593(2):277-83. (PMID: 27562082)
Pharmacogenet Genomics. 2016 May;26(5):243-7. (PMID: 26928270)
PLoS One. 2015 Jun 29;10(6):e0130827. (PMID: 26121033)
Dis Markers. 2010;28(3):137-47. (PMID: 20534900)
J Occup Environ Med. 2012 Sep;54(9):1157-62. (PMID: 22885711)
Pharmacogenomics. 2017 Dec;18(18):1683-1695. (PMID: 29173064)
Int J Cancer. 2001 Aug 15;93(4):584-9. (PMID: 11477564)
Pediatr Blood Cancer. 2012 Jul 15;59(1):144-8. (PMID: 22431292)
Pharmacogenomics. 2015;16(4):323-32. (PMID: 25823781)
Biol Res. 2011;44(1):89-105. (PMID: 21720686)
Nat Genet. 2009 Dec;41(12):1345-9. (PMID: 19898482)
Oncotarget. 2017 Mar 7;8(10):16190-16201. (PMID: 26918827)
Mol Gen Mikrobiol Virusol. 2013;(4):6-9. (PMID: 24645271)
Pharmacogenomics J. 2009 Oct;9(5):347-53. (PMID: 19434073)
EMBO Mol Med. 2017 Jan;9(1):7-26. (PMID: 27794029)
Cell Mol Life Sci. 2000 Dec;57(13-14):1927-37. (PMID: 11215518)
Laryngoscope Investig Otolaryngol. 2017 Mar 16;2(2):69-79. (PMID: 28894825)
Nat Genet. 2015 Mar;47(3):263-6. (PMID: 25665007)
Clin Cancer Res. 1999 Mar;5(3):673-80. (PMID: 10100721)
Clin Pharmacol Ther. 2013 Aug;94(2):252-9. (PMID: 23820299)
Cancer Chemother Pharmacol. 2017 Aug;80(2):287-293. (PMID: 28623449)
J Clin Oncol. 2007 Feb 20;25(6):708-14. (PMID: 17228018)
Pharmacogenomics J. 2017 Dec;17(6):515-520. (PMID: 27457817)
Clin Chem. 2004 Nov;50(11):2012-8. (PMID: 15345661)
Clin Cancer Res. 2018 Apr 15;24(8):1866-1871. (PMID: 29358504)
Anticancer Drugs. 2000 Sep;11(8):639-43. (PMID: 11081456)
Cancer Chemother Rep. 1973 Apr;57(2):191-200. (PMID: 4126381)
Anat Rec (Hoboken). 2012 Nov;295(11):1837-50. (PMID: 23045231)
PLoS One. 2014 Dec 31;9(12):e115869. (PMID: 25551397)
Pharmacogenomics J. 2008 Feb;8(1):23-8. (PMID: 17457342)
J Clin Oncol. 2016 Aug 10;34(23):2687-9. (PMID: 27382103)
Toxicol Lett. 2010 Mar 1;193(1):41-9. (PMID: 20015469)
Neuro Oncol. 2009 Jun;11(3):292-300. (PMID: 18952980)
Cancer. 2016 Jun 1;122(11):1647-58. (PMID: 26859792)
Br J Clin Pharmacol. 2013 Feb;75(2):516-23. (PMID: 22804784)
Cancer Res. 2004 Dec 15;64(24):9217-24. (PMID: 15604295)
J Natl Cancer Inst. 2014 Mar 12;106(5):. (PMID: 24623533)
Anticancer Res. 2003 Mar-Apr;23(2B):1249-55. (PMID: 12820379)
Neoplasma. 2016;63(2):263-8. (PMID: 26774148)
Pharmacogenet Genomics. 2017 Jun;27(6):213-222. (PMID: 28445188)
Indian J Otolaryngol Head Neck Surg. 2011 Apr;63(2):151-4. (PMID: 22468252)
Neuroscience. 2006 Feb;137(3):981-90. (PMID: 16330149)
Clin Cancer Res. 2017 Jul 1;23(13):3325-3333. (PMID: 28039263)
Oncotarget. 2018 Jul 20;9(56):30883-30893. (PMID: 30112115)
J Clin Oncol. 2016 Aug 10;34(23):2712-20. (PMID: 27354478)
Front Cell Neurosci. 2017 Oct 27;11:338. (PMID: 29163050)
Cardiovasc Hematol Agents Med Chem. 2017 Nov 8;15(1):23-30. (PMID: 28552060)
Nat Rev Drug Discov. 2005 Apr;4(4):307-20. (PMID: 15789122)
Tohoku J Exp Med. 2009 Nov;219(3):177-86. (PMID: 19851045)
Toxicol Appl Pharmacol. 2005 May 1;204(3):238-55. (PMID: 15845416)
Lancet. 2017 Dec 2;390(10111):2414. (PMID: 29208294)
J Transl Med. 2007 Dec 27;5:70. (PMID: 18162130)
Neuro Oncol. 2017 Oct 1;19(10):1372-1379. (PMID: 28444219)
Front Aging Neurosci. 2018 Jan 12;9:447. (PMID: 29375369)
Cell Mol Life Sci. 2018 Nov;75(21):4021-4040. (PMID: 29916093)
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14609-14. (PMID: 18794526)
Pediatr Blood Cancer. 2013 Apr;60(4):593-8. (PMID: 23065688)
Lancet. 2017 Dec 2;390(10111):2503-2515. (PMID: 28705460)
Cancer Med. 2015 Nov;4(11):1679-86. (PMID: 26400460)
Hear Res. 2009 Nov;257(1-2):8-15. (PMID: 19643173)
J Pediatr Hematol Oncol. 2013 May;35(4):e138-43. (PMID: 23274376)
J Neurosci. 2015 Dec 16;35(50):16494-503. (PMID: 26674873)
Lung Cancer. 2012 Aug;77(2):438-42. (PMID: 22516052)
Pharmacogenomics. 2014 Sep;15(13):1667-76. (PMID: 25410892)
Hear Res. 2005 Jul;205(1-2):241-8. (PMID: 15953532)
Mol Pharmacol. 2006 Jul;70(1):23-9. (PMID: 16569706)
J Clin Oncol. 2017 Apr 20;35(12):1341-1367. (PMID: 28148207)
Int J Pediatr Otorhinolaryngol. 2016 Nov;90:64-69. (PMID: 27729156)

0 (Antineoplastic Agents)
Q20Q21Q62J (Cisplatin)

Date Created: 20190307 Date Completed: 20200924 Latest Revision: 20200924

20231215

PMC6401165

10.1038/s41598-019-40138-z

30837596