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

He, Yong-Qiao; Wang, Tong-Min; Ji, Mingfang; Mai, Zhi-Ming; Tang, Minzhong; Wang, Ruozheng; Zhou, Yifeng; Zheng, Yuming et al. · Nat Commun · 2022

case_control · Level III

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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<sub>trend</sub> ranging from 2.79 × 10<sup>-7</sup> to 4.79 × 10<sup>-44</sup>). 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.

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