High risk Epstein‐Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma. Issue 12 (7th January 2019)

• Record Type: Journal Article
• Authors: Hui, Kwai Fung; Chan, Tsz Fung; Yang, Wanling; Shen, Jiangshan Jane; Lam, Ki Pui; Kwok, Hin; Sham, Pak C.; Tsao, Sai Wah; Kwong, Dora L.; Lung, Maria Li; Chiang, Alan Kwok Shing
• Is Part Of: International journal of cancer. Volume 144:Issue 12(2019)
• Page Start: 3031
• Page End: 3042
• Publication Date: 2019-01-07
• Subjects: Epstein–Barr virus -- nasopharyngeal carcinoma -- genome‐wide analysis -- sequencing -- EBV‐encoded small RNA -- HKNPC‐EBERvar; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32049
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Whether certain variants of Epstein–Barr virus (EBV) are linked to the pathogenesis of nasopharyngeal carcinoma (NPC), which shows a marked geographic restriction, remains an unresolved issue. We performed a case–control study comparing genomic sequences of EBV isolated from saliva samples of 142 population carriers with those from primary tumour biopsies derived from 62 patients with NPC of Hong Kong. Cluster analysis discovered five EBV subgroups 1A‐C and 2A‐B amongst the population carriers in contrast to the predominance of 1A and ‐B in the majority of NPC. Genome‐wide association study (GWAS) identified a panel of NPC‐associated single nucleotide polymorphisms (SNPs) and indels in the EBER locus. The most significant polymorphism, which can be found in 96.8% NPC cases and 40.1% population carriers of Hong Kong, is a four‐base‐deletion polymorphism downstream of EBER2 (EBER‐del) from coordinates 7188–7191 ( p = 1.91 × 10 −7 ). In addition, the predicted secondary structure of EBER2 is altered with likely functional consequence in nearly all NPC cases. Using the SNPs and indels associated with NPC, genetic risk score is assigned for each EBV variant. EBV variants with high genetic risk score are found to be much more prevalent in Hong Kong Chinese than individuals of other geographic regions and in NPC than other EBV‐associated cancers. We conclude that high risk EBV variants with polymorphisms in the EBER locus, designated as HKNPC‐EBERvar, are strongly associated with NPC. Further investigation of the biological function and potential clinical application of these newly identified polymorphisms in NPC and other EBV‐associated cancers is warranted. Abstract : What's new? Genetic variation in Epstein‐Barr virus appears to play an important role in nasopharyngeal cancer (NPC). These authors conducted a case‐control study in Hong Kong, where NPC incidence is high. They compared EBV genomes from NPC patients with those from population carriers. Population carriers harbored five different EBV types, they found, while only two showed up in tumor samples. A genome‐wide association study identified a four‐base‐deletion in the EBER locus, which occurred in 97% of NPC cases and 40% of population carriers. More research into the geographic distribution of EBV variants could help explain why NPC incidence varies among populations.