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

Yong-Qiao He, Tong-Min Wang, Mingfang Ji, Zhi-Ming Mai, Minzhong Tang, Ruozheng Wang, Yifeng Zhou, Yuming Zheng, Ruowen Xiao, Dawei Yang, Ziyi Wu, Changmi Deng, Jiangbo Zhang, Wenqiong Xue, Siqi Dong, Jiyun Zhan, Yonglin Cai, Fugui Li, Biaohua Wu, Ying Liao, Ting Zhou, Meiqi Zheng, Yijing Jia, Danhua Li, Lianjing Cao, Leilei Yuan, Wenli Zhang, Luting Luo, Xiating Tong, Yanxia Wu, Xizhao Li, Peifen Zhang, Xiaohui Zheng, Shaodan Zhang, Yezhu Hu, Weiling Qin, Bisen Deng, Xuejun Liang, Peiwen Fan, Yaning Feng, Jia Song, Shang-Hang Xie, Ellen T. Chang, Zhe Zhang, Guangwu Huang, Miao Xu, Lin Feng, Guangfu Jin, Jinxin Bei, Sumei Cao, Qing Liu, Zisis Kozlakidis, Haiqiang Mai, Ying Sun, Jun Ma, Zhibin Hu, Jianjun Liu, Maria Li Lung, Hans-Olov Adami, Hongbing Shen (), Weimin Ye (), Tai-Hing Lam (), Yi-Xin Zeng and Wei-Hua Jia ()
Additional contact information
Yong-Qiao He: Sun Yat-sen University Cancer Center
Tong-Min Wang: Sun Yat-sen University Cancer Center
Mingfang Ji: Zhongshan Hospital of Sun Yat-sen University
Zhi-Ming Mai: The University of Hong Kong
Minzhong Tang: Wuzhou Red Cross Hospital
Ruozheng Wang: Chinese Academy of Medical Sciences
Yifeng Zhou: Medical College of Soochow University
Yuming Zheng: Wuzhou Red Cross Hospital
Ruowen Xiao: Sun Yat-sen University Cancer Center
Dawei Yang: Sun Yat-sen University
Ziyi Wu: Sun Yat-sen University Cancer Center
Changmi Deng: Sun Yat-sen University Cancer Center
Jiangbo Zhang: Sun Yat-sen University Cancer Center
Wenqiong Xue: Sun Yat-sen University Cancer Center
Siqi Dong: Sun Yat-sen University Cancer Center
Jiyun Zhan: Public Health Service Center of Xiaolan Town
Yonglin Cai: Wuzhou Red Cross Hospital
Fugui Li: Zhongshan Hospital of Sun Yat-sen University
Biaohua Wu: Zhongshan Hospital of Sun Yat-sen University
Ying Liao: Sun Yat-sen University Cancer Center
Ting Zhou: Sun Yat-sen University Cancer Center
Meiqi Zheng: Sun Yat-sen University Cancer Center
Yijing Jia: Sun Yat-sen University
Danhua Li: Sun Yat-sen University Cancer Center
Lianjing Cao: Sun Yat-sen University Cancer Center
Leilei Yuan: Sun Yat-sen University
Wenli Zhang: Sun Yat-sen University Cancer Center
Luting Luo: Sun Yat-sen University
Xiating Tong: Sun Yat-sen University
Yanxia Wu: Sun Yat-sen University Cancer Center
Xizhao Li: Sun Yat-sen University Cancer Center
Peifen Zhang: Sun Yat-sen University Cancer Center
Xiaohui Zheng: Sun Yat-sen University Cancer Center
Shaodan Zhang: Sun Yat-sen University Cancer Center
Yezhu Hu: Sun Yat-sen University Cancer Center
Weiling Qin: Wuzhou Red Cross Hospital
Bisen Deng: Public Health Service Center of Xiaolan Town
Xuejun Liang: Public Health Service Center of Xiaolan Town
Peiwen Fan: The Third Affiliated Hospital of Xinjiang Medical University
Yaning Feng: Key Laboratory of Oncology of Xinjiang Uyghur Autonomous Region
Jia Song: The Third Affiliated Teaching Hospital of Xinjiang Medical University, Affiliated Cancer Hospital
Shang-Hang Xie: Sun Yat-sen University Cancer Center
Ellen T. Chang: Center for Health Sciences, Exponent, Inc.
Zhe Zhang: First Affiliated Hospital of Guangxi Medical University
Guangwu Huang: First Affiliated Hospital of Guangxi Medical University
Miao Xu: Sun Yat-sen University Cancer Center
Lin Feng: Sun Yat-sen University Cancer Center
Guangfu Jin: Nanjing Medical University
Jinxin Bei: Sun Yat-sen University Cancer Center
Sumei Cao: Sun Yat-sen University Cancer Center
Qing Liu: Sun Yat-sen University Cancer Center
Zisis Kozlakidis: Faculty of Medical Sciences - University College London
Haiqiang Mai: Sun Yat-sen University Cancer Center
Ying Sun: Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy
Jun Ma: Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy
Zhibin Hu: Nanjing Medical University
Jianjun Liu: Agency for Science, Technology and Research (A*STAR)
Maria Li Lung: The University of Hong Kong
Hans-Olov Adami: Institute of Health and Society, University of Oslo
Hongbing Shen: Nanjing Medical University
Weimin Ye: Karolinska Institutet
Tai-Hing Lam: The University of Hong Kong
Yi-Xin Zeng: Sun Yat-sen University Cancer Center
Wei-Hua Jia: Sun Yat-sen University Cancer Center

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.

Date: 2022
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DOI: 10.1038/s41467-022-29570-4

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