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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]

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]

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: The cystic fibrosis transmembrane conductance regulator (CFTR) holds an important role in retaining lung function, but its association with lung cancer is unclear. A case-control study was conducted to determine the possible associations of the genetic variants in the CFTR gene with lung cancer risk. Genotypes of the most common deletion ΔF508, one functional SNP, and eight tag SNPs in the CFTR gene were determined in 574 lung cancer patients and 679 controls. A logistic regression model, adjusting for known risk factors, was used to evaluate the association of each variant with lung cancer risk, as confirmation haplotype and sub-haplotype analyses were performed. ΔF508 deletion and genotypes with minor alleles in one tag SNP, rs10487372, and one functional SNP, rs213950, were inversely associated with lung cancer risk. The results of haplotype and sub-haplotype analyses were consistent with single variant analysis, all pointing to deletion ΔF508 being the key variant for significant haplotypes and sub-haplotypes. Individuals with ‘deletion-T’ (ΔF508/rs10487372) haplotype had a 68% reduced risk for lung cancer compared to common haplotype ‘no-deletion-C’ (OR=0.32; 95% CI=0.15–0.68; p =0.01). Genetic variations in the CFTR gene might modulate the risk of lung cancer. This study, for the first time, provides evidence of a protective role of the CFTR deletion carrier in the etiology of lung cancer. [ABSTRACT FROM AUTHOR]

Summary: Background: Lung cancer in individuals who have never smoked tobacco products is an increasing medical and public-health issue. We aimed to unravel the genetic basis of lung cancer in never smokers. Methods: We did a four-stage investigation. First, a genome-wide association study of single nucleotide polymorphisms (SNPs) was done with 754 never smokers (377 matched case-control pairs at Mayo Clinic, Rochester, MN, USA). Second, the top candidate SNPs from the first study were validated in two independent studies among 735 (MD Anderson Cancer Center, Houston, TX, USA) and 253 (Harvard University, Boston, MA, USA) never smokers. Third, further replication of the top SNP was done in 530 never smokers (UCLA, Los Angeles, CA, USA). Fourth, expression quantitative trait loci (eQTL) and gene-expression differences were analysed to further elucidate the causal relation between the validated SNPs and the risk of lung cancer in never smokers. Findings: 44 top candidate SNPs were identified that might alter the risk of lung cancer in never smokers. rs2352028 at chromosome 13q31.3 was subsequently replicated with an additive genetic model in the four independent studies, with a combined odds ratio of 1·46 (95% CI 1·26–1·70, p=5·94×10−6). A cis eQTL analysis showed there was a strong correlation between genotypes of the replicated SNPs and the transcription level of the gene GPC5 in normal lung tissues (p=1·96×10−4), with the high-risk allele linked with lower expression. Additionally, the transcription level of GPC5 in normal lung tissue was twice that detected in matched lung adenocarcinoma tissue (p=6·75×10−11). Interpretation: Genetic variants at 13q31.3 alter the expression of GPC5, and are associated with susceptibility to lung cancer in never smokers. Downregulation of GPC5 might contribute to the development of lung cancer in never smokers. Funding: US National Institutes of Health; Mayo Foundation. [Copyright &y& Elsevier]