Epstein‐Barr virus seroreactivity among unaffected individuals within high‐risk nasopharyngeal carcinoma families in Taiwan

Pickard, Amy; Chen, Chien-Jen; Diehl, Scott R.; Liu, Meiying; Cheng, Yiping; Hsu, Wan‐Lun; Sun, Brenda; Hsu, Mow‐Ming; Chen, I-How; Chen, Jen‐Yang; Yang, Czau‐Siung; Mittl, Beth; Chou, Sheng-Ping; Ruggles, Deborah D.; Goldstein, Alisa M.; Hildesheim, Allan

doi:10.1002/ijc.20222

Cited by 55 publications

(64 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Each study participant was asked to consent to the collection of 30 mL blood for genotyping and EBV antibody testing. Serum was tested for antibody titers to several anti-EBV antibodies known to be associated with NPC, including viral capsid antigen IgA, EBV nuclear antigen 1 IgA, and anti-DNase antibodies, according to the methods described previously (22). Individuals positive for any of these EBV markers were considered seropositive and individuals negative to all were classified as seronegative.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Risk Factors for Nasopharyngeal Carcinoma in High-Risk Nasopharyngeal Carcinoma Families in Taiwan

Yang

Diehl²,

Pfeiffer³

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

Self Cite

227

View full text Add to dashboard Cite

A study of nasopharyngeal carcinoma (NPC) families with two or more affected members was conducted in Taiwan (265 families with 2,444 individuals, 502 affected and 1,942 unaffected) to determine the association between NPC and potential etiologic factors in NPC high-risk families. Similar to results from a previous case-control study in Taiwan, Guangdong salted fish consumption during childhood, exposure to wood, and betel nut consumption were all associated with elevated NPC risk using conditional logistic regression, although these associations were not as strong as in the case-control study possibly due to shared environment among family members. Risk associated with cumulative wood exposure and salted fish consumption before age 10 was stronger in families with early NPC age-onset [odds ratio (OR wood ), 5.10; 95% confidence interval (95% CI), 1.50-17.34; OR fish , 3.94; 95% CI, 1.47-10.55] or three or more affected members (OR wood , 4.41; 95% CI, 1.58-12.30; OR fish , 4.27; 95% CI, 1.10-16.47). In contrast, a tendency for elevated risk was noted for betel nut use in late age-onset families (OR, 2.44; 95% CI, 1.16-5.13) and the CYP2E1 c2 allele in families with less than three affected members (OR, 2.06; 95% CI, 1.04-3.35). Risk estimates associated with these exposures were similar when the analyses were restricted to EBV-seropositive subjects. To better adjust for degree of relationship among family members and residual genetic correlations, we also calculated ORs using a variance components model. The results from the two methods were similar indicating that the risk estimates from conditional logistic regression were unbiased. (Cancer Epidemiol Biomarkers Prev 2005;14(4):900 -5)

show abstract

Section: Methodsmentioning

confidence: 99%

Evaluation of Risk Factors for Nasopharyngeal Carcinoma in High-Risk Nasopharyngeal Carcinoma Families in Taiwan

Yang

Diehl²,

Pfeiffer³

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

Self Cite

227

View full text Add to dashboard Cite

show abstract

“…The first was a casecontrol study, 20 and the second was a study of families with 2 or more affected members. 19,21 The 2 studies were conducted by the same collaborating institutions (the U.S. NIH and National Taiwan University) and used similar data collection instruments and testing methods. Human subject review committees in Taiwan and the United States approved both projects.…”

Section: Study Populationmentioning

confidence: 99%

“…Our data demonstrated that unaffected individuals from high-risk NPC families had elevated anti-EBV antibody titers compared to levels in the community at large. 19 In the current study, we evaluated EBV load in sera from unaffected individuals in high-risk NPC families. Our goal was to define the levels of EBV load that characterize this high-risk population using 2 different molecular assays.…”

mentioning

confidence: 99%

Distribution of Epstein‐Barr viral load in serum of individuals from nasopharyngeal carcinoma high‐risk families in Taiwan

Yang

Goldstein

Chen

et al. 2005

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

The utility of EBV load as a tumor marker in nasopharyngeal carcinoma (NPC) patients suggests that it might also serve as a screening test for individuals who are at high risk for developing NPC. We previously demonstrated that unaffected individuals from high-risk families had elevated anti-EBV antibody levels compared to community controls. In this study, we measured EBV load using 2 different real-time PCR assays (targeting BamH1W and polymerase gene sequences, respectively) carried out in 2 independent research labs in serum samples from 19 untreated NPC cases, 11 healthy community controls and 100 unaffected individuals from families in which 2 or more individuals were affected with NPC. EBV genomes were detectable in 68% of NPC cases by the EBV BamH1W assay and in 74% by the EBV polymerase assay (kappa = 0.64). Patients with stage III or IV disease had significantly higher EBV load compared to those with stage I or II disease (p = 0.008). EBV DNA was detected in a single community control sample by the EBV BamH1W assay and in none of the samples by the EBV polymerase assay. Only one of 100 unaffected family members tested positive by both assays. An additional 14 were positive by only one of the 2 EBV load assays used and usually in only one of the duplicate wells tested, all with very low viral loads (3-50 copies/ml). In addition, EBV load did not correlate with EBV serology results (anti-VCA, anti-DNase, anti-EBNA-1) among these unaffected family members. In conclusion, our study suggests limited clinical utility of the EBV load test, in its current configuration, to screen individuals from high-risk families. Should a more sensitive or specific molecular assay be developed that is capable of detecting and distinguishing tumor-derived EBV genomes or gene products from true negatives, it could be evaluated as a possible screening tool for asymptomatic and early-stage NPC.

show abstract

“…EBV enters B cells by interaction of the major glycoprotein gp350/220 (BLLF1) with CD 21 and then penetrates by the complex of viral glycoproteins gp25 (Pickard et al , 2004), gp42/38 and gp85 (gH) (Tao et al, 2006). Furthermore, EBV glycoproteins play important roles in humoral immune responses and sera against these proteins often neutralize virus.…”

Section: Introductionmentioning

confidence: 99%

Antibodies against Epstein–Barr virus gp78 antigen: a novel marker for serological diagnosis of nasopharyngeal carcinoma detected by xMAP technology

Xie

et al. 2008

Journal of General Virology

View full text Add to dashboard Cite

Immunoglobulin (Ig) A and/or IgG reactivities to several Epstein-Barr virus (EBV) antigens have been used to facilitate diagnosis of nasopharyngeal carcinoma (NPC). However, antibodies against gp78, an EBV membrane glycoprotein, have not been examined to this day. In this study, we utilized Luminex multi-analyte profiling (xMAP) technology to analyse antibody responses to a synthetic peptide of gp78 in sera samples from 95 NPC patients and 91 healthy controls. Our results showed the sensitivity and specificity of IgA-gp78 for NPC diagnosis were 79 and 71 %, respectively, while those of IgG-gp78 were 74 and 73 %, respectively. The IgA and IgG responses to different EBV antigens were not identical within an individual and IgA-gp78 and IgG-gp78 could be complementary to antibodies against viral capsid antigen (VCA), the diffused early antigen (EA-D) and the nuclear antigen EBNA1 for NPC diagnosis. When the six EBV parameters for NPC prediction, i.e. IgA-gp78, IgG-gp78, IgA-VCA, IgA-EBNA1, IgA-EA-D and IgG-EA-D, are combined, the combined predictors were able to reach overall sensitivity and specificity of 91 and 95 %, respectively. Thus, simultaneous detection of these EBV serological markers could improve the predictive values of NPC using xMAP technology. INTRODUCTIONEpstein-Barr virus (EBV) is a ubiquitous gammaherpes virus composed of a protein core enclosed by DNA, an inner nucleocapsid with 162 capsomeres, a middle protein tegument, and an outer envelope carrying various membrane glycoproteins (Dolyniuk et al., 1976;Epstein et al., 1965;Khanna et al., 1995). EBV infects more than 90 % of the population worldwide and usually establishes a lifelong persistence in the host (Cohen, 2000). Most populations get primary infection in childhood and are asymptomatic, but Westerners whose primary infection is delayed until adolescence may develop infectious mononucleosis (Amon & Farrell, 2005). More strikingly, the virus is associated with a spectrum of cancers presenting endemic features, such as Burkitt's lymphoma in Africa and nasopharyngeal carcinoma (NPC) in Southern China and South-East Asia (Pattle & Farrell, 2006;Raab-Traub et al., 1987).EBV is closely correlated with NPC, which could be reflected by consistent expression of EBV gene products in NPC tumour cells and general elevation of serum antibody levels against EBV antigens in NPC patients (Busson et al., 2004;Gastpar et al., 1981;Henle & Henle, 1976;Old et al., 1966;Raab-Traub, 2002). In comparison with healthy EBV carriers, NPC patients typically show strong IgG and especially IgA reactivities to lytic antigens (Fachiroh et al., 2004;Henle & Henle, 1976), so an EBV serological assay could facilitate diagnosis and prognosis of NPC. IgA antibody titres against the EBV viral capsid antigen (VCA) and the diffused early antigens (EA-D) are regularly tested in many clinical centres (Deng et al., 1995; Hadar et al., 1986;Henle & Henle, 1976;Ho et al., 1998 et al., 2004). However, few of them have been shown as valuable markers for NPC diagnosis. gp350/220 is t...

show abstract

Epstein‐Barr virus seroreactivity among unaffected individuals within high‐risk nasopharyngeal carcinoma families in Taiwan

Cited by 55 publications

References 39 publications

Evaluation of Risk Factors for Nasopharyngeal Carcinoma in High-Risk Nasopharyngeal Carcinoma Families in Taiwan

Evaluation of Risk Factors for Nasopharyngeal Carcinoma in High-Risk Nasopharyngeal Carcinoma Families in Taiwan

Distribution of Epstein‐Barr viral load in serum of individuals from nasopharyngeal carcinoma high‐risk families in Taiwan

Antibodies against Epstein–Barr virus gp78 antigen: a novel marker for serological diagnosis of nasopharyngeal carcinoma detected by xMAP technology

Contact Info

Product

Resources

About