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

He, Yong; Liao, Xiaoyu; Xue, Wen; Xu, Ya; Xu, Feng; Li, Fang Fang; Li, Xi Zhao; Zhang, Jiang Bo; Wang, Tong Min; Wang, Fang; Yu, Huan; Feng, Qi Sheng; Chen, Li Zhen; Cao, Su Mei; Liu, Qing; Mu, Jianbing; Jia, Wei Hua

doi:10.1093/infdis/jiy542

Cited by 25 publications

(31 citation statements)

References 49 publications

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“…These findings indicate that the interaction between herbal medicine and EBV is biologically plausible and herbal medicine might involve in the pathogenesis of NPC either though reactivating EBV or through a promotional effect on cells transformed by EBV. However, we have observed a positive association between monthly consumption of Canton‐style herbal tea and oral EBV DNA loads in healthy population . In this study, we further validated the association by identifying the positive relationships between consumption of Canton‐style herbal tea and serum VCA‐IgA and EA‐IgA antibodies in NPC patients, especially in older patients, females, those less educated and those with a family history of tumors.…”

Section: Discussionsupporting

confidence: 54%

“…However, we have observed a positive association between monthly consumption of Canton-style herbal tea and oral EBV DNA loads in healthy population. 25 In this study, we further validated the association by identifying the positive relationships between consumption of Canton-style herbal tea and serum VCA-IgA and EA-IgA antibodies in NPC patients, especially in older patients, females, those less educated and those with a family history of tumors. Our results add to the evidence for the hypothesis that herbal tea may increase the risk of NPC by promoting the reactivation of EBV.…”

Section: Discussionmentioning

confidence: 75%

“…Our previous in vitro experiment found cigarette smoke extract could promote EBV lytic gene expression in B cells . Further, our previous large‐scale multicenter epidemiological study observed positive relationships between smoking and serum seropositivity for VCA‐IgA, EBNA1‐IgA and Zta‐IgA, as well as oral EBV DNA loads among healthy individuals, especially those in areas with high NPC incidence. These results suggest that smoking may increase the potential NPC risk by triggering the EBV reactivation.…”

Section: Discussionmentioning

confidence: 86%

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Associations between environmental factors and serological Epstein‐Barr virus antibodies in patients with nasopharyngeal carcinoma in South China

Zhou

Yang

et al. 2019

Cancer Medicine

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Epstein‐Barr virus (EBV) reactivation, reflected by aberrantly increased levels of various serological antibodies, has been suggested to be an early indicator of nasopharyngeal carcinoma (NPC) onset and progression. We have previously suggested that certain lifestyle and dietary factors were associated with elevated serological levels of the antibody against various EBV antigens namely VCA, Zta, EBNA1, and oral EBV DNA loads among healthy population. It remains unclear whether these potential environmental factors would also influence EBV serological antibodies in NPC patients. We conducted an epidemiological study to evaluate the associations between such environmental factors and EBV antibody levels among 1701 NPC patients in South China. Pretreatment serums were collected and examined for VCA‐IgA and EA‐IgA by immunoenzymatic assays and antienzyme rate (AER) of EBV DNase‐specific neutralizing antibody. We found that consumption of Canton‐style herbal tea was significantly correlated with increased serological antibody levels of VCA‐IgA and EA‐IgA, with adjusted ORs of 1.35 (95% CI: 1.03‐1.76) and 1.32 (95% CI: 1.01‐1.73), respectively, in the weekly intake frequency stratum, while not related to AER of EBV DNase‐specific neutralizing antibody. Smoking was found to be not only an apparent risk factor for higher antibody levels of AER in stage III‐IV patients (OR = 1.60, 95% CI: 1.11‐2.30), but also associated closely with NPC stage at diagnosis (OR = 2.17, 95% CI: 1.47‐3.22), with dose‐response effects. In conclusion, we found consumption of Canton‐style herbal tea and cigarette smoking were in positive associations with elevated EBV antibodies in NPC patients, which may be of public health significance for the primary prevention of EBV‐associated diseases especially NPC.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 86%

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Associations between environmental factors and serological Epstein‐Barr virus antibodies in patients with nasopharyngeal carcinoma in South China

Zhou

Yang

et al. 2019

Cancer Medicine

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“…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.…”

Section: Methodsmentioning

confidence: 99%

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

Miao

Wang

Liao

et al. 2020

Journal of Medical Virology

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Nasopharyngeal carcinoma (NPC), the most common head and neck cancer, is characterized by distinct geographic distribution and familial aggregation. Multiple risk factors, including host genetics, environmental factor, and EBV infection, have been linked to the development of NPC, particularly in the familial clustering cases. However, the cause of NPC endemicity remains enigmatic due possibly to the complicated interplay between these risk factors. Recently, positive Epstein‐Barr virus (EBV) DNA loads at nasopharyngeal (NP) cavity has been found to reflect NPC development and applied in NPC screening. To examine whether the increased NP EBV loads could aggregate in the families and be affected by host genetics and environmental factor, EBV loads were obtained by 510 NP brushing samples from eligible unaffected individuals, who have two or more relatives affected with NPC, in 116 high‐risk NPC families. The correlation of relative pairs was estimated using S.A.G.E. (version 6.4, 2016), and host heritability of NP EBV loads was calculated with variance component models using SOLAR (version 8.4.2, 2019). In result, significant correlations of EBV loads were observed between parent‐offspring pairs and sibling‐sibling pairs (P < .001), but not in distant kin relationship pairs. Interestingly, after excluding the shared environmental factor within families, host genetics contributes significantly to NP EBV loads with a heritability of 56.41% (P = 1.00 × 10−7), and its effect was slightly elevated (68.86%, P = 3.40 × 10−6) in families with more NPC cases (≥3). These findings indicate that additional host‐genetic variants involved in the EBV local NP mucosal behavior may be especially important for the development of NPC.

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“…The virus may be reactivated during periods of environmental stress, whereby the EBV antibodies against viral antigens become elevated. Smokers have higher levels of anti-EBV antibodies 26,27 and higher EBV viral load 28,29 compared to nonsmokers, and several studies indicate that smoking may trigger EBV reactivation 30,31 .…”

Section: Discussionmentioning

confidence: 99%

Smoking and Epstein–Barr virus infection in multiple sclerosis development

Hedström

Huang

Brenner

et al. 2020

Sci Rep

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It is unclear whether smoking interacts with different aspects of Epstein-Barr virus (EBV) infection with regard to multiple sclerosis (MS) risk. We aimed to investigate whether smoking acts synergistically with elevated EBNA-1 antibody levels or infectious mononucleosis (IM) history regarding MS risk. Two Swedish population-based case-control studies were used (6,340 cases and 6,219 matched controls). Subjects with different smoking, EBNA-1 and IM status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). Current and past smokers had higher EBNA-1 antibody levels than never smokers (p < 0.0001). There was an additive interaction between current smoking and high EBNA-1 antibody levels (AP 0.3, 95% CI 0.2-0.4), but not between past smoking and high EBNA-1 antibody levels (AP 0.01, 95% CI − 0.1 to 0.1), with regard to MS risk. An interaction also occurred between current smoking and IM history (AP 0.2, 95% CI 0.004-0.4), but not between past smoking and IM history (AP − 0.06, 95% CI − 0.4 to 0.3). Current smoking increases EBNA-1 antibody levels and acts synergistically with both aspects of EBV infection to increase MS risk, indicating that there is at least one pathway to disease in which both risk factors are involved. Multiple sclerosis (MS) is an inflammatory disease of the central nervous system with underlying genetic and environmental factors. Smoking, high levels of EBNA-1 Immunoglobulin G (IgG), and infectious mononucleosis (IM) history have consistently been associated with increased MS risk 1-3. Previous studies on the interplay between smoking and aspects of EBV infection have used different study designs and statistical methods, and sample sizes have often been limited which may have contributed to conflicting results (Table 1). The first study observed a positive interaction on the multiplicative scale between smoking and elevated EBNA-1 IgG levels with regard to MS risk 4. Smoking was only observed to increase MS risk among subjects with high EBNA-1 IgG levels. These findings were not replicated in other studies 5-7. A recent study showed a trend towards a negative interaction among young adults and a trend towards a positive interaction among older subjects, as defined by age at EBV assessment, suggesting age may influence the interaction between smoking and EBNA-1 IgG levels 8. Results from previous studies on a possible interaction between smoking and IM history have also been conflicting. Two studies found no interaction between smoking and IM history 6,7 , whereas a recent study reported a negative interaction on the multiplicative scale regarding MS risk 9. Using two Swedish population-based case-control studies comprising 6,340 cases and 6,219 controls, we aimed to investigate the interplay between smoking and different aspects of EBV infection [elevated EBNA-1 IgG levels and infectious monon...

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

Cited by 25 publications

References 49 publications

Associations between environmental factors and serological Epstein‐Barr virus antibodies in patients with nasopharyngeal carcinoma in South China

Associations between environmental factors and serological Epstein‐Barr virus antibodies in patients with nasopharyngeal carcinoma in South China

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

Smoking and Epstein–Barr virus infection in multiple sclerosis development

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