Association of Clinical Aspects and Genetic Variants with the Severity of Cisplatin-Induced Ototoxicity in Head and Neck Squamous Cell Carcinoma: A Prospective Cohort Study

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Mar 29

PMID 36980643

Authors

Ligia Traldi Macedo

Ericka Francislaine Dias Costa

Bruna Fernandes Carvalho

Gustavo Jacob Lourenco

Luciane Calonga

Arthur Menino Castilho

Carlos Takahiro Chone

Carmen Silvia Passos Lima

Affiliations

Soon will be listed here.

Abstract

Background: Cisplatin (CDDP) is a major ototoxic chemotherapy agent for head and neck squamous cell carcinoma (HNSCC) treatment. Clinicopathological features and genotypes encode different stages of CDDP metabolism, as their coexistence may influence the prevalence and severity of hearing loss.

Methods: HNSCC patients under CDDP chemoradiation were prospectively provided with baseline and post-treatment audiometry. Clinicopathological features and genetic variants encoding glutathione S-transferases (GSTT1, GSTM1, GSTP1), nucleotide excision repair (XPC, XPD, XPF, ERCC1), mismatch repair (MLH1, MSH2, MSH3, EXO1), and apoptosis (P53, CASP8, CASP9, CASP3, FAS, FASL)-related proteins were analyzed regarding ototoxicity.

Results: Eighty-nine patients were included, with a cumulative CDDP dose of 260 mg/m. Moderate/severe ototoxicity occurred in 26 (29%) patients, particularly related to hearing loss at frequencies over 3000 Hertz. Race, body-mass index, and cumulative CDDP were independent risk factors. Patients with specific isolated and combined genotypes of , c.313A>G, c.2815A>C, c.934G>A, c.1762G>A, c.3133A>G, c.-844A>T, and c.215G>C SNVs had up to 32.22 higher odds of presenting moderate/severe ototoxicity.

Conclusions: Our data present, for the first time, the association of combined inherited nucleotide variants involved in CDDP efflux, DNA repair, and apoptosis with ototoxicity, which could be potential predictors in future clinical and genomic models.

References

Vermorken J, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M . Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007; 357(17):1695-704. DOI: 10.1056/NEJMoa071028. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Sibley K, Rollinson S, Allan J, Smith A, Law G, Roddam P . Functional FAS promoter polymorphisms are associated with increased risk of acute myeloid leukemia. Cancer Res. 2003; 63(15):4327-30. View

Moyer A, Salavaggione O, Hebbring S, Moon I, Hildebrandt M, Eckloff B . Glutathione S-transferase T1 and M1: gene sequence variation and functional genomics. Clin Cancer Res. 2007; 13(23):7207-16. DOI: 10.1158/1078-0432.CCR-07-0635. View

Miaskowski C, Paul S, Mastick J, Abrams G, Topp K, Smoot B . Associations Between Perceived Stress and Chemotherapy-Induced Peripheral Neuropathy and Otoxicity in Adult Cancer Survivors. J Pain Symptom Manage. 2018; 56(1):88-97. PMC: 6015523. DOI: 10.1016/j.jpainsymman.2018.02.021. View

Goode E, Ulrich C, Potter J . Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 2002; 11(12):1513-30. View

Driessen C, Ham J, Te Loo M, van Meerten E, van Lamoen M, Hakobjan M . Genetic Variants as Predictive Markers for Ototoxicity and Nephrotoxicity in Patients with Locally Advanced Head and Neck Cancer Treated with Cisplatin-Containing Chemoradiotherapy (The PRONE Study). Cancers (Basel). 2019; 11(4). PMC: 6520709. DOI: 10.3390/cancers11040551. View

Laurell G . Pharmacological intervention in the field of ototoxicity. HNO. 2019; 67(6):434-439. PMC: 6538585. DOI: 10.1007/s00106-019-0663-1. View

Siddik Z . Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene. 2003; 22(47):7265-79. DOI: 10.1038/sj.onc.1206933. View

10.

Levine M, Ensom M . Post hoc power analysis: an idea whose time has passed?. Pharmacotherapy. 2001; 21(4):405-9. DOI: 10.1592/phco.21.5.405.34503. View

11.

Dumont P, Leu J, Della Pietra 3rd A, George D, Murphy M . The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet. 2003; 33(3):357-65. DOI: 10.1038/ng1093. View

12.

Nomura K, Nakao M, Morimoto T . Effect of smoking on hearing loss: quality assessment and meta-analysis. Prev Med. 2004; 40(2):138-44. DOI: 10.1016/j.ypmed.2004.05.011. View

13.

Oken M, Creech R, Tormey D, Horton J, Davis T, McFadden E . Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 5(6):649-55. View

14.

Clemens E, Broer L, Langer T, Uitterlinden A, de Vries A, van Grotel M . Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach: The International PanCareLIFE Study. Pharmacogenomics J. 2019; 20(2):294-305. DOI: 10.1038/s41397-019-0113-1. View

15.

Terrier P, Townsend A, Coindre J, Triche T, Cowan K . An immunohistochemical study of pi class glutathione S-transferase expression in normal human tissue. Am J Pathol. 1990; 137(4):845-53. PMC: 1877535. View

16.

Pincinato E, Visacri M, de Souza C, Tuan B, Ferrari G, de Oliveira D . Impact of drug formulation and free platinum/cisplatin ratio on hypersensitivity reactions to cisplatin: formulation matters. J Clin Pharm Ther. 2014; 40(1):41-7. DOI: 10.1111/jcpt.12220. View

17.

Hayes J, Flanagan J, Jowsey I . Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005; 45:51-88. DOI: 10.1146/annurev.pharmtox.45.120403.095857. View

18.

Spitz M, Wu X, Wang Y, Wang L, Shete S, Amos C . Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res. 2001; 61(4):1354-7. View

19.

Lydiatt W, Patel S, OSullivan B, Brandwein M, Ridge J, Migliacci J . Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017; 67(2):122-137. DOI: 10.3322/caac.21389. View

20.

Wang M, Xu S . Statistical power in genome-wide association studies and quantitative trait locus mapping. Heredity (Edinb). 2019; 123(3):287-306. PMC: 6781134. DOI: 10.1038/s41437-019-0205-3. View