4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-022-29570-4

Keywords

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Funding

  1. National Key Research and Development Program of China [2021YFC2500405, 2020YFC1316900]
  2. Basic and Applied Basic Research Foundation of Guangdong Province, China [2021B1515420007]
  3. Science and Technology Planning Project of Guangzhou, China [201804020094, 201904010467]
  4. Sino-Sweden Joint Research Program [81861138006]
  5. Special Support Program for High-level Professionals on Scientific and Technological Innovation of Guangdong Province, China [2014TX01R201]
  6. National Natural Science Foundation of China [81973131, 81903395, 82003520, 81803319, 81802708]
  7. National Science Fund for Distinguished Young Scholars of China [81325018]
  8. Key Area Research and Development Program of Guangdong Province, China [2019B110233004]
  9. Sun Yat-sen University [84000-31143413]
  10. Science and Technology Planning Project of Guangdong Province, China
  11. Hong Kong Research Grants Council Area of Excellence Scheme [AoE/M-06/08]
  12. World Cancer Research Fund UK
  13. Wereld Kanker Onderzoek Funds (WCRF NL), as part of the WCRF International Grant Program [2011/460]
  14. Wuzhou science and technology grant, China [20151036]

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The authors developed a polygenic risk score (PRS) for nasopharyngeal carcinoma using a large-scale genome-wide association study, which improved risk stratification and personalized screening.
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 x 10(-7) to 4.79 x 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. Polygenic Risk Scores (PRS) show promise for facilitating cancer risk stratification. Here, the authors performed a large genome-wide association study and develop a PRS for nasopharyngeal carcinoma, which could improve risk stratification and personalized screening.

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