Clinical and Genome-wide Association Analysis of Chemoradiation-induced Hearing Loss in Nasopharyngeal Carcinoma

Overview

Journal Hum Genet

Specialty Genetics

Date 2023 Apr 16

PMID 37062025

Authors

Yong-Qiao He

Lu-Ting Luo

Tong-Min Wang

Wen-Qiong Xue

Da-Wei Yang

Dan-Hua Li

Hua Diao

Ruo-Wen Xiao

Chang-Mi Deng

Wen-Li Zhang

Ying Liao

Yan-Xia Wu

Qiao-Ling Wang

Ting Zhou

Xi-Zhao Li

Xiao-Hui Zheng

Pei-Fen Zhang

Shao-Dan Zhang

Ye-Zhu Hu

Ying Sun

Wei-Hua Jia

Affiliations

Soon will be listed here.

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). 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.

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