A polygenic risk score (PRS) can identify patients at high risk of developing nasopharyngeal carcinoma (NPC) with relatively good performance, according to researchers. 

Combining the PRS with Epstein-Barr virus (EBV) antibody testing improved NPC risk stratification and informed personalized screening, the researchers wrote in Nature Communications.

To create the PRS, the researchers performed a genome-wide association study (GWAS). They constructed and validated the PRS using data from 6 patient populations, which included a total of 6059 NPC cases and 7582 control individuals. Four of the patient populations were used for the discovery stage (constructing the score), and 2 were used for the replication stage (validating the score).

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The GWAS revealed 6 new human leukocyte antigen (HLA) single nucleotide polymorphisms (SNPs) contributing to NPC risk:

  • rs3131875 (ZFP57/HLA-F: odds ratio [OR], 1.97; P =1.66×10−39)
  • rs1611163 (upstream of HLA-G: OR, 0.54; P =1.39×10−32
  • rs9357092 (ZNR1ASP: OR, 2.04; P =8.74×10−48), 
  • rs2596506 (HLA-B downstream: OR, 0.54; P =4.67×10−37), 
  • rs2844484 (NFKBIL1/LTA: OR, 0.64; P =5.46× 10−24
  • rs9268644 (HLA-DRA: OR, 0.65; P =1.61×10−14).

The 6 newly identified SNPs and 6 previously identified SNPs were integrated into the PRS model. The model enabled the identification of high-risk NPC patients with an area under the curve (AUC) of 0.65 in the combined samples (all 6 cohorts). The AUC was 0.66 for the discovery stage and 0.64 for the replication stage.

Combining the PRS and EBV Test

The researchers observed an improvement in screening when they combined the PRS with the anti-EBV immunoglobulin A test. The positive predictive value (PPV) of the EBV test alone was 4.84%. 

When the EBV test was combined with the PRS, the PPV was 7.99% for seropositive patients in the top 20% of genetic risk based on the PRS, which was defined as 13 seropositive patients screened to detect 1 incident NPC. 

The PPV was 8.38% for patients in the top 10% (12 seropositive patients screened) and 11.91% for the top 5% (8 seropositive patients screened).

Of the 27,657 patients who were classified as having a low risk of NPC by EBV serology, 19 patients missed diagnosis by EBV tests and developed NPC during follow-up. 

The researchers found that 8 of the 19 cases (42.11%) were in the top 10% of the PRS, and 18 of the 19 cases (94.7%) were in the top 50%. In a cohort with these 19 EBV-seronegative cases and 1118 randomly selected non-cancer controls, the AUC of the PRS was 0.82.

Lifetime Risk of NPC

The researchers also used the PRS to calculate the average cumulative risk of developing NPC during one’s lifetime (between 20 and 80 years). The risk was 2.74% for men and 0.83% for women. However, for patients in the top 1% of genetic risk based on the PRS, the corresponding cumulative risk was 7.79% for men and 2.19% for women. 

Based on their findings, the researchers recommended starting NPC screening at the age of 22 years for men in the top 10% of genetic risk based on the PRS and at age 40 for men in the bottom 10%. 

The recommended starting age was 30 years for women in the top 10%. However, women in the bottom 50% did not reach the risk threshold in their lifetime, according to the researchers.

“The PRS could identify high-risk individuals who would benefit from screening and inform clinical decisions of whether and when to participate in NPC screening for a given individual,” the researchers concluded.


He YQ, Wang TM, Ji M, et al. A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening. Nat Commun. Published online April 12, 2022. doi:10.1038/s41467-022-29570-4