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

Author:

He Yong-Qiao,Wang Tong-MinORCID,Ji Mingfang,Mai Zhi-Ming,Tang Minzhong,Wang Ruozheng,Zhou YifengORCID,Zheng Yuming,Xiao Ruowen,Yang Dawei,Wu Ziyi,Deng Changmi,Zhang Jiangbo,Xue Wenqiong,Dong Siqi,Zhan Jiyun,Cai YonglinORCID,Li Fugui,Wu Biaohua,Liao Ying,Zhou Ting,Zheng Meiqi,Jia Yijing,Li Danhua,Cao Lianjing,Yuan Leilei,Zhang Wenli,Luo Luting,Tong Xiating,Wu Yanxia,Li Xizhao,Zhang Peifen,Zheng Xiaohui,Zhang Shaodan,Hu Yezhu,Qin Weiling,Deng Bisen,Liang Xuejun,Fan Peiwen,Feng Yaning,Song Jia,Xie Shang-Hang,Chang Ellen T.,Zhang ZheORCID,Huang Guangwu,Xu MiaoORCID,Feng LinORCID,Jin GuangfuORCID,Bei JinxinORCID,Cao Sumei,Liu Qing,Kozlakidis ZisisORCID,Mai HaiqiangORCID,Sun YingORCID,Ma Jun,Hu ZhibinORCID,Liu JianjunORCID,Lung Maria Li,Adami Hans-OlovORCID,Shen HongbingORCID,Ye WeiminORCID,Lam Tai-HingORCID,Zeng Yi-XinORCID,Jia Wei-HuaORCID

Abstract

AbstractPolygenic 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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