The Role of NK Cells in EBV Infection and EBV-Associated NPC.

A vast majority of the population worldwide are asymptomatic carriers of Epstein-Barr Virus (EBV). However, some infected individuals eventually develop EBV-related cancers, including Nasopharyngeal Carcinoma (NPC). NPC is one of the most common EBV-associated epithelial cancers, and is highly prevalent in Southern China and Southeast Asia. While NPC is highly sensitive to radiotherapy and chemotherapy, there is a lack of effective and durable treatment among the 15%-30% of patients who subsequently develop recurrent disease. Natural Killer (NK) cells are natural immune lymphocytes that are innately primed against virus-infected cells and nascent aberrant transformed cells. As EBV is found in both virally infected and cancer cells, it is of interest to examine the NK cells' role in both EBV infection and EBV-associated NPC. Herein, we review the current understanding of how EBV-infected cells are cleared by NK cells, and how EBV can evade NK cell-mediated elimination in the context of type II latency in NPC. Next, we summarize the current literature about NPC and NK cell biology. Finally, we discuss the translational potential of NK cells in NPC. This information will deepen our understanding of host immune interactions with EBV-associated NPC and facilitate development of more effective NK-mediated therapies for NPC treatment.

Evaluation of three polygenic risk score models for the prediction of breast cancer risk in Singapore Chinese.

Genome-wide association studies (GWAS) have proven highly successful in identifying single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. The majority of these studies are on European populations, with limited SNP association data in other populations. We genotyped 51 GWAS-identified SNPs in two independent cohorts of Singaporean Chinese. Cohort 1 comprised 1294 BC cases and 885 controls and was used to determine odds ratios (ORs); Cohort 2 had 301 BC cases and 243 controls for deriving polygenic risk scores (PRS). After age-adjustment, 11 SNPs were found to be significantly associated with BC risk. Five SNPs were present in <1% of Cohort 1 and were excluded from further PRS analysis. To assess the cumulative effect of the remaining 46 SNPs on BC risk, we generated three PRS models: Model-1 included 46 SNPs; Model-2 included 11 statistically significant SNPs; and Model-3 included the SNPs in Model-2 but excluded SNPs that were in strong linkage disequilibrium with the others. Across Models-1, -2 and -3, women in the highest PRS quartile had the greatest ORs of 1.894 (95% CI = 1.157-3.100), 2.013 (95% CI = 1.227-3.302) and 1.751 (95% CI = 1.073-2.856) respectively, suggesting a direct correlation between PRS and BC risk. Given the potential of PRS in BC risk stratification, our findings suggest the need to tailor the selection of SNPs to be included in an ethnic-specific PRS model.