Decreased oral Epstein‐Barr virus DNA loads in patients with nasopharyngeal carcinoma in Southern China: A case‐control and a family‐based study

Abstract

The link of nasopharyngeal carcinoma (NPC) with Epstein‐Barr virus (EBV) has been established for decades. Although an abnormal high level of EBV sero‐antibody spectrum and cell‐free circulating EBV DNA loads were exhibited in NPC patients, oral EBV DNA loads, which are primarily responsible for the EBV transmission, has not been previously studied in NPC patients. We conducted an epidemiological study to measure the oral EBV loads, viral components, and the relationship with the serum antibody titers in a large case‐control population (968 cases and 1656 controls) and a family‐based population (91 cases and 165 unaffected family members). EBV DNA loads were detected by quantitative PCR approach targeting the BamHI‐W region. Although a large individualized variation existed, we still observed a decreased oral EBV DNA loads in the population of NPC patients compared to that of healthy controls (ORs were 1.00, 0.69, 0.62, 0.33 classified by the quartiles of viral loads, P trend < .001) and family members. In contrast, the elevated levels of oral EBV loads were present in asymptomatic males and elders, suggesting a different important source for EBV transmission. Notably, oral EBV loads were inversely associated with serum antibody titers of VCA‐IgA, EA‐IgA (All P trend < .001) in the cases but not in the controls. Our study provides the first epidemiological data of oral EBV loads and viral components in NPC patients and controls in the highest risk area of Southern China, indicating that NPC status is unlikely to be an important determinant of EBV transmission.

Genome sequencing analysis identifies Epstein–Barr virus subtypes associated with high risk of nasopharyngeal carcinoma

“…Because of the essential role of BALF2 in EBV lytic DNA replication, these amino acid changes may influence the productive lytic cycle of EBV by alternating the function of BALF2 . This is consistent with our observation as well as others 31 that the oral EBV abundance is lower in the NPC cases than the controls. In addition, we also observed the trend of decrease in oral EBV DNA load associated with the EBV subtype carrying the high-risk BALF2 haplotype, although this association is only marginally significant with a huge variation of saliva viral load among individuals.…”

Nasopharyngeal Epstein‐Barr virus DNA loads in high‐risk nasopharyngeal carcinoma families: Familial aggregation and host heritability

“…NP brushing DNA was extracted by an automated workstation (Chemagic Star; Hamilton Robotic, Bonaduz, GR, Switzerland) using the protocol recommended by the manufacturer. EBV DNA loads were detected by real‐time quantitative polymerase chain reaction (qPCR) as described in the previous studies 16‐18 . In brief, qPCR was performed for amplification targeting the BamHI‐W region of EBV genome and a dual‐labeled fluorescence probe was used for hybridization.…”

“…EBV DNA loads were detected by real-time quantitative polymerase chain reaction (qPCR) as described in the previous studies. [16][17][18] In brief, qPCR was performed for amplification targeting the BamHI-W region of EBV genome and a dual-labeled fluorescence probe was used for hybridization. The qPCR assay was conducted in 384-well plates including negative control and all samples tested in duplicate.…”

Association Between Environmental Factors and Oral Epstein-Barr Virus DNA Loads: A Multicenter Cross-sectional Study in China

“…All samples were collected and processed by standard procedures. Oral EBV loads were quantified by real-time quantitative polymerase chain reaction (PCR) as the number of EBV DNA copies per milliliter in mouthwash or saliva specimens (Supplementary Materials) [29][30][31]. The sensitivity of real-time quantitative PCR (5 copies per reaction) was calculated by a standard serial dilution of DNA ( Supplementary Figure 1).…”