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Clinical and genome-wide association analysis of chemoradiation-induced hearing loss in nasopharyngeal carcinoma.

ABSTRACT: Chemoradiation-induced hearing loss (CRIHL) is one of the most devasting side effects for nasopharyngeal carcinoma (NPC) patients, which seriously affects survivors' long-term quality of life. However, few studies have comprehensively characterized the risk factors for CRIHL. In this study, we found that age at diagnosis, tumor stage, and concurrent cisplatin dose were positively associated with chemoradiation-induced hearing loss. We performed a genome-wide association study (GWAS) in 777 NPC patients and identified rs1050851 (within the exon 2 of NFKBIA), a variant with a high deleteriousness score, to be significantly associated with hearing loss risk (HR = 5.46, 95% CI 2.93-10.18, P = 9.51 × 10^-08). The risk genotype of rs1050851 was associated with higher NFKBIA expression, which was correlated with lower cellular tolerance to cisplatin. According to permutation-based enrichment analysis, the variants mapping to 149 hereditary deafness genes were significantly enriched among GWAS top signals, which indicated the genetic similarity between hereditary deafness and CRIHL. Pathway analysis suggested that synaptic signaling was involved in the development of CRIHL. Additionally, the risk score integrating genetic and clinical factors can predict the risk of hearing loss with a relatively good performance in the test set. Collectively, this study shed new light on the etiology of chemoradiation-induced hearing loss, which facilitates high-risk individuals' identification for personalized prevention and treatment.

SUBMITTER: He YQ

PROVIDER: S-EPMC10182145 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Clinical and genome-wide association analysis of chemoradiation-induced hearing loss in nasopharyngeal carcinoma.

He Yong-Qiao YQ Luo Lu-Ting LT Wang Tong-Min TM Xue Wen-Qiong WQ Yang Da-Wei DW Li Dan-Hua DH Diao Hua H Xiao Ruo-Wen RW Deng Chang-Mi CM Zhang Wen-Li WL Liao Ying Y Wu Yan-Xia YX Wang Qiao-Ling QL Zhou Ting T Li Xi-Zhao XZ Zheng Xiao-Hui XH Zhang Pei-Fen PF Zhang Shao-Dan SD Hu Ye-Zhu YZ Sun Ying Y Jia Wei-Hua WH

Human genetics 20230416 6

Chemoradiation-induced hearing loss (CRIHL) is one of the most devasting side effects for nasopharyngeal carcinoma (NPC) patients, which seriously affects survivors' long-term quality of life. However, few studies have comprehensively characterized the risk factors for CRIHL. In this study, we found that age at diagnosis, tumor stage, and concurrent cisplatin dose were positively associated with chemoradiation-induced hearing loss. We performed a genome-wide association study (GWAS) in 777 NPC p ...[more]

PMID: 37062025

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Project description:ObjectiveTo evaluate the clinical efficacy and safety of hydrogen inhalation in improving hearing loss in patients with long-term survival of nasopharyngeal carcinoma after radiotherapy.MethodsThe eustachian tube dysfunction score, pure tone air conduction threshold, bone conduction threshold, the score of tympanogram and otoscope were prospectively observed in patients with deafness after radiotherapy only or combined radiotherapy and chemotherapy for nasopharyngeal carcinoma. Paired t test and one-way analysis of variance were used to analyze the data before and after treatment.ResultsA total of 17 patients were observed. The median time from radiotherapy to now was 228 months, and the median time from the diagnose of deafness to now was 92 months. After 4 weeks of hydrogen inhalation, the score of eustachian tube dysfunction, air conduction and bone conduction hearing thresholds were significantly reduced, P values were 0.0293, 0.0027, 0.0404, respectively. The mean air-bone gap, the score of otoendoscopy and tympanogram were also decreased, but the differences were not significant (P = 0.2079, P = 0.0536, P = 0.1056). Patients with radiotherapy alone and concurrent chemo-radiotherapy had significantly lower air conduction hearing threshold after hydrogen absorption (P = 0.0142, P = 0.0495). The results of air and bone hearing thresholds before, 4 and 12 weeks after hydrogen inhalation showed a descending trend. The air and bone hearing thresholds before hydrogen inhalation were 74.69 ± 27.03 dB and 45.70 ± 21.58 dB, respectively. At the 12th week, the mean values of air and bone hearing thresholds were the lowest, which were 66.88 ± 20.88 dB and 40.94 ± 18.93 dB, respectively, but there was no significant difference in air and bone hearing thresholds among all groups (P = 0.6755, P = 0.7712). After hydrogen inhalation treatment, no adverse reactions such as nosebleed, chest pain, dyspnea, nausea, vomiting, dizziness, earache and allergic reaction were observed.ConclusionThis is the first prospective study on the effect of hydrogen inhalation on hearing improvement in patients with deafness after radiotherapy/chemotherapy for nasopharyngeal carcinoma, suggesting that continuous hydrogen inhalation may be an alternative rehabilitation therapy for these patients.

Dataset Information

Clinical and genome-wide association analysis of chemoradiation-induced hearing loss in nasopharyngeal carcinoma.

Publications

Clinical and genome-wide association analysis of chemoradiation-induced hearing loss in nasopharyngeal carcinoma.

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