A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening

He, Yanhu; Wang, Tong‐Min; Ji, Mingfang; Mai, Zhiming; Tang, Minzhong; Wang, Ruozheng; Zhou, Yifeng; Zheng, Yuming; Xiao, Ruo‐Wen; Yang, Dawei; Wu, Ziyi; Deng, Chang‐Mi; Zhang, Jiangbo; Xue, Wen‐Qiong; Dong, Siqi; Zhan, Jiyun; Cai, Yonglin; Li, Fugui; Wu, Biaohua; Liao, Ying; Zhou, Ting; Miao, Zheng; Jia, Yijing; Li, Dan‐Hua; Cao, Longhui; Yuan, Lei‐Lei; Zhang, Wenli; Luo, Lu‐Ting; Tong, Xia‐Ting; Wu, Yanxia; Li, Xizhao; Zhang, Peifen; Zheng, Xiaohui; Zhang, Shaodan; Hu, Ye‐Zhu; Qin, Weiling; Deng, Bisen; Liang, Xuejun; Fan, Peng; Feng, Yu; Song, Jia; Xie, Shiwei; Chang, Ellen T.; Zhang, Zhe; Huang, Guangwu; Xu, Miao; Feng, Lin; Jin, Guangfu; Bei, Jin‐Xin; Cao, Su‐Mei; Liu, Qing; Kozlakidis, Zisis; Mai, Hai‐Qiang; Sun, Ying; Ma, Jun; Hu, Zhibin; Liu, Jing; Lung, Maria Li; Adami, Hans‐Olov; Shen, Hongbing; W, Ye; Lam, Tai Hing; Zeng, Yi‐Xin; Jia, Wei‐Hua

doi:10.1038/s41467-022-29570-4

Cited by 31 publications

(41 citation statements)

References 49 publications

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“… 7 , 8 , 9 Of note, it has been suggested that PRS could also serve as a biomarker of disease outcomes, but the actual prognostic value of PRS in clinical practice has not been fully assessed. 10 , 11 , 12 Survival probability is a direct measure of cancer prognosis that is clinically important for patients suffering from cancer, 13 it, however, remains undetermined whether PRS can be utilized to predict cancer survival.…”

Section: Introductionmentioning

confidence: 99%

Prognostic evaluation of polygenic risk score underlying pan-cancer analysis: evidence from two large-scale cohorts

Xin¹,

Jiang²,

Li³

et al. 2023

eBioMedicine

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Section: Introductionmentioning

confidence: 99%

Prognostic evaluation of polygenic risk score underlying pan-cancer analysis: evidence from two large-scale cohorts

Xin¹,

Jiang²,

Li³

et al. 2023

eBioMedicine

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“…A standard quality control protocol for genotypes was implemented in PLINK v1.9. The detailed information about genotyping and quality control was described in our previous study (He et al 2022 ). Individuals with call rate < 95%, gender discrepancy, extreme heterozygosity rate (inbreeding coefficient F > 6 SDs), or pairwise identify by descent (IBD) > 0.25 were removed from the analysis.…”

Section: Methodsmentioning

confidence: 99%

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

Luo

Wang

et al. 2023

Hum Genet

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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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“…As a group I carcinogen, EBV causes around 2% of all cancer cases worldwide every year, typically including NPC, EBV-associated lymphomas, and EBVaGC (Young and Dawson, 2014;Yin et al, 2019;He et al, 2022). Recent study has also identified that long-term EBV infection results in chronic inflammatory demyelinating disease of the central nervous system, such as multiple sclerosis (Bjornevik et al, 2022;Bordon, 2022;Robinson and Steinman, 2022;Sollid, 2022).…”

Section: Ebv Infection In Tumorigenesismentioning

confidence: 99%

EBV Infection and Its Regulated Metabolic Reprogramming in Nasopharyngeal Tumorigenesis

Yang

You

Meng³

et al. 2022

Front. Cell. Infect. Microbiol.

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Viral oncogenes may drive cellular metabolic reprogramming to modulate the normal epithelia cell malignant transformation. Understanding the viral oncogene–mediated signaling transduction dysregulation that involves in metabolic reprogramming may provide new therapeutic targets for virus-associated cancer treatment. Latent EBV infection and expression of viral oncogenes, including latent membrane proteins 1 and 2 (LMP1/2), and EBV-encoded BamH I-A rightward transcripts (BART) microRNAs (miR-BARTs), have been demonstrated to play fundamental roles in altering host cell metabolism to support nasopharyngeal carcinoma (NPC) pathogenesis. Yet, how do EBV infection and its encoded oncogenes facilitated the metabolic shifting and their roles in NPC carcinogenesis remains unclear. In this review, we will focus on delineating how EBV infection and its encoded oncoproteins altered the metabolic reprograming of infected cells to support their malignances. Furthermore, based on the understanding of the host’s metabolic signaling alterations induced by EBV, we will provide a new perspective on the interplay between EBV infection and these metabolic pathways and offering a potential therapeutic intervention strategy in the treatment of EBV-associated malignant diseases.

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A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening

Cited by 31 publications

References 49 publications

Prognostic evaluation of polygenic risk score underlying pan-cancer analysis: evidence from two large-scale cohorts

Prognostic evaluation of polygenic risk score underlying pan-cancer analysis: evidence from two large-scale cohorts

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

EBV Infection and Its Regulated Metabolic Reprogramming in Nasopharyngeal Tumorigenesis

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