A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
Yong‐Qiao He, Tong‐Min Wang, Mingfang Ji, Zhiming Mai, Minzhong Tang, Ruozheng Wang, Yifeng Zhou, Yuming Zheng, Ruowen Xiao, Dawei Yang, Ziyi Wu, Changmi Deng, Jiangbo Zhang, Wen‐Qiong Xue, Siqi Dong, Jiyun Zhan, Yonglin Cai, Fugui Li, Biaohua Wu, Ying Liao, Ting Zhou, Mei‐Qi Zheng, Yijing Jia, Dan‐Hua Li, Lianjing Cao, Leilei Yuan, Wenli Zhang, Lu‐Ting Luo, Xia‐Ting Tong, Yanxia Wu, Xizhao Li, Pei‐Fen Zhang, Xiao‐Hui Zheng, Shaodan Zhang, Ye‐Zhu 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, Jin‐Xin Bei, Su‐Mei Cao, Qing Liu, Zisis Kozlakidis, Hai‐Qiang Mai, Ying Sun, Jun Ma, Zhibin Hu, Jianjun Liu, Maria Li Lung, Hans‐Olov Adami, Hongbing Shen, Weimin Ye, TH Lam, Yi‐Xin Zeng, Wei‐Hua Jia
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 ( P trend 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.