听力损失
鼻咽癌
生物
全基因组关联研究
肿瘤科
病因学
内科学
遗传学
生物信息学
基因
基因型
听力学
单核苷酸多态性
医学
放射治疗
作者
Yanhu He,Lu‐Ting Luo,Tongmin Wang,Wen‐Qiong Xue,Dawei Yang,Dan‐Hua Li,Hua Diao,Ruowen Xiao,Chang‐Mi Deng,Wenli Zhang,Ying Liao,Yanxia Wu,Qiaoling Wang,Ting Zhou,Xi‐Zhao Li,Xiaohui Zheng,Peifen Zhang,Shaodan Zhang,Ye‐Zhu Hu,Ying Sun,Wei‐Hua Jia
出处
期刊:Human Genetics
[Springer Nature]
日期:2023-04-16
卷期号:142 (6): 759-772
标识
DOI:10.1007/s00439-023-02554-0
摘要
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.
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