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Background: Gene polymorphism rs1048369 of glypican-4 (GPC4) gene has been reported to be significantly different between Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) and EBV-negative GC. However, little is known about the polymorphism in nasopharyngeal carcinoma (NPC), which is a malignant tumor with a high prevalence of EBV. Objective: The distribution of GPC4 polymorphism rs1048369 was investigated in NPC patients, especially in those with EBV infection. The association between the polymorphism of GPC4 and the susceptibility to EBV-positive and EBV-negative NPC was also explored. Patients and Methods: The GPC4 gene polymorphism rs1048369 was detected in 143 cases of EBV-positive NPC and in 19 cases of EBV-negative NPC using polymerase chain reaction. One hundred and seven peripheral blood samples from healthy individuals were also measured as a control group. Results: The difference in genotype CC between EBV-positive NPC patients and healthy individuals was significant (χ2 = 15.273, p < 0.01). No significant difference was observed between EBV-positive and EBV-negative NPC cases. Between EBV-negative NPC cases and healthy individuals, there was no significant difference in GPC4 gene polymorphism in both genotypic and allelic frequencies. Conclusions: The GPC4 gene polymorphism is associated with susceptibility to EBV-positive NPC. The CC genotype of GPC4 may represent a risk factor for NPC in Northern China. [ABSTRACT FROM AUTHOR]

Background/Aims: Aquaporins are widely expressed in a variety of cancers and were found to play an important role in cell migration, angiogenesis, tumor formation, and tumor development. Thus, they have been proposed as a potential biomarker for some cancers. Accordingly, we analyzed the association between a single-nucleotide polymorphism locus of aquaporin 3 (rs2231231) and Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (EBVaNPC), lymphoma (EBVaL), and gastric carcinoma in China. Methods: Sequenom MassARRAY technique and polymerase chain reaction sequencing were used to test the genotype of 393 cases of patients with cancer and 148 normal control (NC) samples. A χ2 test or correction for continuity or the likelihood ratio was used for statistical analysis, and two-sided p values < 0.05 were considered a statistically significant difference. Results: We found that the genotype distributions were significantly different between either the EBVaNPC group and the NC group or the EBVaL case group and the NC group. However, no statistical associations between rs2231231 and gastric carcinoma was observed in the current study. Conclusions: The AQP3 gene polymorphism is associated with a susceptibility to EBVaNPC and EBVaL, and the homozygous AA genotype is more frequently observed in individuals who develop EBVaNPC and EBVaL. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to characterize the specific Epstein-Barr virus (EBV) polymorphisms from nasopharyngeal carcinoma (NPC) patients and healthy donors in Southern China, and to explore the relationship between EBV genotypes and NPC. Methods: The EBNA-2 gene of 32 EBV-positive NPCs and 39 EBV-positive throat washing (TW) samples from healthy individuals from Southern China was analyzed using PCR and sequencing. Results: We found E2-A to be the predominant subtype in Southern China. The distribution of EBNA-2 subtypes between NPCs and TWs was significantly different (p < 0.01) and the E2-A subtype was overly represented in NPCs. Conclusions: E2-A is the predominant subtype in Southern China, and the distribution of EBNA-2 subtypes between NPCs and TWs is significantly different. In Southern China, the E2-A subtype is significantly more frequent in NPCs than TWs, and is also more common than in Northern China. This suggests that the E2-A subtype may play an important role in the pathogenesis of NPC and that EBNA-2 gene variations are tumor-specific polymorphisms. [ABSTRACT FROM AUTHOR]

To characterize the sequence variation and the potential implication of the Epstein-Barr virus (EBV) oncogene in lymphoma, BamHI-C fragment rightward reading frame 1 (BCRF1) was sequenced in different types of EBV-positive lymphoma in northern China, and polymorphisms were compared with previous variation data from other malignancies. The dominate subtype of BCRF1 in EBV-positive lymphoma was the B95-8 prototype, and a mutation in the signal peptide was more strongly associated with Hodgkin's lymphoma. The high conservation of BCRF1 in EBV-positive lymphoma suggests its important role in maintaining the basic biological activity and immunosuppressive functions of the virus. [ABSTRACT FROM AUTHOR]

Gastric cancer including the cardia and non-cardia types is the second frequent cause of cancer-related deaths worldwide. A subset of non-cardia gastric cancer genetic susceptibility loci have been addressed among Asian through genome-wide association studies (GWASs). This study was to evaluate the effects of single nucleotide polymorphisms (SNPs) of long intergenic non-coding RNAs (lincRNAs) on non-cardia gastric cancer susceptibility in Chinese populations. We selected long intergenic noncoding RNAs (lincRNAs) located in non-cardia gastric cancer risk-related loci and identified 10 SNPs located within lincRNA exonic regions. We examined whether genetic polymorphisms in lincRNAs exons are associated with non-cardia gastric cancer risk in 438 non-cardia gastric cancer patients and 727 control subjects in Chinese populations using logistic regression. Functional relevance was further examined by biochemical assays. We found that lincRNA-NR_024015 rs8506AA carrier was significantly associated with risk of non-cardia gastric cancer (adjusted odds ratio [OR] = 1.56, 95%CI = 1.03–2.39, compared with the rs8506 AG or GG genotype. Further stratification analysis showed that the risk effect was more pronounced in subgroups of smokers (P = 0.001). Biochemical analysis demonstrated that the G to A base change at rs8506G>A disrupts the binding site for has-miR-526b, thereby influencing the transcriptional activity of lincRNA-NR_024015 and affecting cell proliferation. Our present study established a robust association between the rs8506G>A polymorphism in the lincRNA-NR_024015 exon and the risk of non-cardia gastric cancer. [ABSTRACT FROM AUTHOR]

The Epstein-Barr virus (EBV) nuclear antigen protein 3A (EBNA-3A), a protein of 944 amino acids, is one of five EBNAs (EBNA-1, -2, -LP, -3A and -3C) essential for conversion of primary B lymphocytes to lymphoblastoid cell lines. To characterize the variations of the EBNA-3A gene and explore the association between EBNA-3A gene variations and EBV-associated diseases, we sequenced the key regions of EBNA-3A in the isolates of 30 EBV-associated gastric carcinomas (EBVaGCs), 44 nasopharyngeal carcinomas (NPCs) and 48 samples from healthy donors in northern China. We found that EBNA-3A shares a common evolutionary origin with isolates from southern China and Japan but has the character of a geographical variant. Based on a phylogenetic tree, all of the samples can be subdivided into three patterns, named 3A-8, 3A-5 and B95-8-like. The distribution of EBNA-3A subtypes among EBVaGC, NPC and healthy donors is not significantly different. The subtype 3A-8 is predominant not only in northern China but also in southern China; it is a geographically associated polymorphism in China. [ABSTRACT FROM AUTHOR]

In most previous studies, comparisons of Epstein-Barr virus (EBV) gene polymorphisms and genotypes were made between strains from tumors and normal throat washings (TWs) from different individuals. However, it remains controversial whether different EBV subtypes are present in different parts of the same NPC patient. In order to address this question, in this study, we compared the genotypes in sets of paired throat washings (TW) and paraffin-embedded tissues of 20 patients with nasopharyngeal carcinoma (NPC), and we found the same genotype in throat washings (TWs) and tumor cells from the same individual in most cases. The subtypes of EBER and EBNA1 genes were furthermore sequenced, and identical EBV strains were identified in tumor tissues and TWs. In conclusion, different sites of the same individual are infected by the same EBV strains, except for a few differences in occasional cases, suggesting that the EBV subtype detected in throat washings is a reasonable guide to the subtype present in the carcinoma tissue. [ABSTRACT FROM AUTHOR]

To characterize the sequence variation of the gp350/220 and explore its potential association with EBV-associated tumors, the gp350/220 gene was sequenced from 41 EBV-associated gastric carcinoma (EBVaGC) and 81 nasopharyngeal carcinoma (NPC) biopsies as well as 35 throat washing (TW) samples from healthy donors. Preferential linkages between variants of the N-terminus of gp350/220 and EBNA3C variants were detected, and type A/BLLF1-a was the dominant variant in this study. The dominant variant in the C-terminal region of gp350/220 was 9P. The similar distribution of gp350/220 variants in NPC, EBVaGC and healthy donors suggest that gp350/220 variations are geographically restricted rather than tumor-specific polymorphisms. [ABSTRACT FROM AUTHOR]

Abstract: Epstein-Barr virus (EBV) BZLF1 gene can trigger EBV from latent infection to lytic replicative phase. The functions of BZLF1 are well known, while little is known about its gene polymorphism. In order to elucidate the sequence variations of BZLF1 and its association with malignancies, we analyzed BZLF1 gene in 24 EBV-associated gastric carcinomas, 41 nasopharyngeal carcinomas and 24 throat washing samples from healthy donors in Northern China using PCR-direct sequencing method. Three types and 8 subtypes of BZLF1 were identified. A dominant type BZLF1-A was found in 67 of 89 (75.3%) isolates. Type BZLF1-B was characterized by a common Ala deletion at residue 127, which was detected in 21 of 89 isolates (23.6%). Type BZLF1-C contained only one isolate (GC103), which had the same sequence with the prototype B95-8. Among 3 functional domains of BZLF1 protein, the transactivation domain had most mutations, followed by the bZIP domains (the DNA binding domain and dimerization domain). No prevalence of any subtypes or mutations in the functional domains among three specimen groups was found (P > 0.05). Our study indicates that BZLF1 subtypes and amino acid changes in functional domains are not preferentially associated with EBV-associated gastric carcinomas or nasopharyngeal carcinomas in Northern China. BZLF1 gene variations are geographically restricted rather than tumor-specific polymorphisms. [Copyright &y& Elsevier]

Objectives: To characterize the specific Epstein-Barr virus (EBV) polymorphisms from nasopharyngeal carcinoma (NPC) patients and healthy donors in Northern China, and to explore the relationship between the EBV genotypes and NPC. Methods: The genotypes of EBV strains were analyzed by the polymerase chain reaction and restriction fragment length polymorphism. Results: The predominant EBV type was A, C or F in both NPC and healthy individuals. The distributions of the EBV subtypes between NPC and healthy donors were not significantly different (p > 0.05). The frequency of type f strains in NPC was significantly lower in Northern China than in Southern China. Conclusions: No evidence of special EBV genotypes associated with NPC was found, suggesting that EBV strains derived from the NPC patients may reflect geographic distribution rather than being NPC restricted. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

As a member of the Bam HI-A rightward transcripts family of the Epstein-Barr virus (EBV), RPMS1 expression has been confirmed in all EBV-associated tumors. However, few studies have investigated the single-nucleotide polymorphisms (SNPs) of RPMS1 , and only one SNP site (g155391a) has been reported to be associated with nasopharyngeal carcinoma occurrence. The objective of this study was to investigate the polymorphism of RPMS1 in EBV-associated tumors (gastric carcinoma, nasopharyngeal carcinoma, and lymphoma). In this research, nested-PCR was performed to analyze DNA sequences of 420 EBV-associated samples. Phylogenetic analysis revealed four RPMS1 genotypes (RPMS1-A, RPMS1-B, RPMS1-C, and RPMS1-D). A significant difference ( p  < 0.05) among northern and southern China samples was observed. Furthermore, there was a significant difference between EBV-associated tumors and healthy controls for RPMS1 ( p  < 0.05). These findings demonstrated that RPMS1 variation was not only tumor-specific but also geographically restricted in EBV-associated samples. [ABSTRACT FROM AUTHOR]

Background/aims Gastric cancer (GC) is one of the most common malignant tumors in China and single nucleotide polymorphisms (SNPs) have been found to be highly related to GC carcinogenesis. Glypican-4 (GPC4), a member of the heparan sulphate proteoglycan family, plays an important role in the regulation of cell growth and differentiation. However, little is known about polymorphisms of GPC4 gene and their associated susceptibility to GC, especially to Epstein-Barr virus-associated GC (EBVaGC). Here we studied the GPC4 polymorphism (rs1048369) in GC individuals, especially those with EBVaGC, and we explored an association between the GPC4 gene polymorphism (rs1048369) and susceptibility to EBVaGC and Epstein-Barr virus-negative GC (EBVnGC) in a population from Northern China. Patients and methods The GPC4 gene polymorphism (rs1048369) was detected in 54 cases of EBVaGC and 73 cases of EBVnGC using polymerase chain reaction (PCR). One hundred and seven peripheral blood samples from healthy individuals were also measured as a control group. Results There were significant differences in both the genotype and allelic frequency of GPC4 gene (rs1048369) between the EBVaGC and EBVnGC patients. Meanwhile, the distribution of genotype and allelic frequency of GPC4 (rs1048369) differed between EBVaGC and control groups. Distribution of the GPC4 genotype also revealed differences between EBVnGC and control groups, no significant differences in the allelic frequency of the GPC4 gene (rs1048369) were observed. The frequency of the T allele in EBVaGC group was significantly higher than that in control and EBVnGC groups. Conclusions The GPC4 gene polymorphism and the allele of GPC4 are both associated with susceptibility to EBVaGC. The T allele of GPC4 may represent a risk factor for EBVaGC. [ABSTRACT FROM AUTHOR]

Abstract: The Epstein–Barr virus (EBV) BamHI-A rightward frame 1 (BARF1) gene is frequently expressed in EBV-associated epithelial malignancies and involves in oncogenicity and immunomodulation. To characterize the variations of BARF1 gene in different populations, the sequences of BARF1 gene in Northern Chinese nasopharyngeal carcinoma (NPC), EBV-associated gastric carcinoma (EBVaGC) and healthy donors were analyzed. The correlation of BARF1 variation with polymorphisms of BamHI F fragment (type F and f variants) and EBV-coded viral interleukin-10 (vIL-10) gene (B95-8 and SPM patterns) was also explored. Two major subtypes of BARF1 gene, designated as B95-8 and V29A, were identified. B95-8 subtype had identical amino acid sequence to B95-8 and was the dominant subtype among the EBV isolates from Northern China. V29A subtype, with one consistent amino acid change at residue 29 (V→A) and several nucleotide changes, showed higher frequency in NPC cases (25.3%, 20/79) than in EBVaGC cases (0/45) or healthy donors (4.3%, 2/46) (NPC vs. EBVaGC: P =0.0001; NPC vs. healthy donor: P =0.004). A preferential linkage between BamHI F and BARF1/vIL-10 polymorphisms was found. Type f isolates was specially correlated with the V29A/SPM genotype in NPC isolates and type f/V29A/SPM was preferentially found in NPC. BARF1/c-fms homology domain, transforming domain and cytotoxic T lymphocyte (CTL) epitopes of BARF1 were highly conserved in most isolates, suggesting the important role of BARF1 in virus infection and the potential usefulness in EBV-targeting immunotherapy of EBV-associated tumors. The relatively higher prevalence of type f/V29A/SPM strains in NPC may also suggest the association between these variations in multiple viral genes and NPC. [Copyright &y& Elsevier]

Abstract: The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1), the only viral protein consistently expressed in all EBV-associated tumors, is classified into five distinct subtypes: P-ala, P-thr, V-leu, V-val and V-pro based on the signature changes at amino acid residue 487. By now, whether the EBNA1 subtypes preferentially associate with particular malignancies or represent geographical polymorphism remains controversial. In China, most studies of the EBNA1 variations focused on nasopharyngeal carcinoma (NPC) in endemic area, among which some suggested the V-val subtype is preferentially associated with NPC. To characterize the variations of EBNA1 in NPC non-endemic area in China and to explore the association of EBNA1 variations with EBV-associated gastric carcinoma (EBVaGC) and NPC, the C-terminal sequences of EBNA1 were analyzed for 41 EBVaGC, 41 NPC biopsies and 55 throat washing (TW) samples from healthy donors in Northern China. Three major patterns of the EBNA1 variations, V-val, P-thrV and V-leuV, were observed, and V-val was the most common subtype in all the three groups, followed by P-thrV and V-leuV. The distribution of the EBNA1 subtypes among EBVaGC, NPC and healthy donors was not significantly different (P >0.05). In addition, preferential linkages between EBNA1 subtypes and EBNA3C variants were found to exist. There was no evidence that particular EBNA1 subtypes are preferentially associated with EBVaGC or NPC in Northern China, suggesting that EBNA1 gene variations are geographically restricted rather than tumor-specific polymorphisms. [Copyright &y& Elsevier]