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A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma.
- Source :
-
Chinese journal of cancer [Chin J Cancer] 2015 Dec 16; Vol. 34 (12), pp. 563-72. Date of Electronic Publication: 2015 Dec 16. - Publication Year :
- 2015
-
Abstract
- Background: Epstein-Barr virus (EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma (NPC), which has a high incidence in certain regions. This study aimed to address how EBV variations contribute to the risk of NPC.<br />Methods: Using logistic regression analysis and based on the sequence variations at EBV-encoded RPMS1, a multi-stage association study was conducted to identify EBV variations associated with NPC risk. A protein degradation assay was performed to characterize the functional relevance of the RPMS1 variations.<br />Results: Based on EBV-encoded RPMS1 variations, a single nucleotide polymorphism (SNP) in the EBV genome (locus 155391: G>A, named G155391A) was associated with NPC in 157 cases and 319 healthy controls from an NPC endemic region in South China [P < 0.001, odds ratio (OR) = 4.47, 95% confidence interval (CI) 2.71-7.37]. The results were further validated in three independent cohorts from the NPC endemic region (P < 0.001, OR = 5.20, 95% CI 3.18-8.50 in 168 cases vs. 241 controls, and P < 0.001, OR = 5.27, 95% CI 4.06-6.85 in 726 cases vs. 880 controls) and a non-endemic region (P < 0.001, OR = 7.52, 95% CI 3.69-15.32 in 58 cases vs. 612 controls). The combined analysis in 1109 cases and 2052 controls revealed that the SNP G155391A was strongly associated with NPC (P(combined) < 0.001, OR = 5.27, 95% CI 4.31-6.44). Moreover, the frequency of the SNP G155391A was associated with NPC incidence but was not associated with the incidences of other EBV-related malignancies. Furthermore, the protein degradation assay showed that this SNP decreased the degradation of the oncogenic RPMS1 protein.<br />Conclusions: Our study identified an EBV variation specifically and significantly associated with a high risk of NPC. These findings provide insights into the pathogenesis of NPC and strategies for prevention.
- Subjects :
- Adult
Aged
Carcinoma
Case-Control Studies
China epidemiology
Epstein-Barr Virus Infections complications
Epstein-Barr Virus Infections epidemiology
Female
Genetic Association Studies
Genome, Viral
Herpesvirus 4, Human isolation & purification
Humans
Incidence
Male
Middle Aged
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms epidemiology
Pilot Projects
Risk Assessment methods
Tumor Cells, Cultured
Epstein-Barr Virus Infections virology
Herpesvirus 4, Human genetics
Nasopharyngeal Neoplasms virology
Neoplasm Proteins genetics
Polymorphism, Single Nucleotide
Viral Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1000-467X
- Volume :
- 34
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Chinese journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 26675171
- Full Text :
- https://doi.org/10.1186/s40880-015-0073-z