Clinical and genome-wide association analysis of chemoradiation-induced hearing loss in nasopharyngeal carcinoma
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Published:2023-04-16
Issue:6
Volume:142
Page:759-772
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ISSN:0340-6717
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Container-title:Human Genetics
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language:en
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Short-container-title:Hum Genet
Author:
He Yong-Qiao,Luo Lu-Ting,Wang Tong-Min,Xue Wen-Qiong,Yang Da-Wei,Li Dan-Hua,Diao Hua,Xiao Ruo-Wen,Deng Chang-Mi,Zhang Wen-Li,Liao Ying,Wu Yan-Xia,Wang Qiao-Ling,Zhou Ting,Li Xi-Zhao,Zheng Xiao-Hui,Zhang Pei-Fen,Zhang Shao-Dan,Hu Ye-Zhu,Sun Ying,Jia Wei-Hua
Abstract
AbstractChemoradiation-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.
Funder
National Key Research and Development Program of China Basic and Applied Basic Research Foundation of Guangdong Province, China Special Support Program for High-level Professionals on Scientific and Technological Innovation of Guangdong Province, China National Natural Science Foundation of China Key Area Research and Development Program of Guangdong Province, China
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
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