A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma

Fu-Tuo Feng, Qian Cui, Wen-Sheng Liu, Yun-Miao Guo, Qi-Sheng Feng, Li-Zhen Chen, Miao Xu, Bing Luo, Da-Jiang Li, Li-Fu Hu, Jaap M Middeldorp, Octavia Ramayanti, Qian Tao, Su-Mei Cao, Wei-Hua Jia, Jin-Xin Bei, Yi-Xin Zeng

Research output: Contribution to journalArticleAcademicpeer-review

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.

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.

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.

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.

Original languageEnglish
Article number61
Pages (from-to)563-72
Number of pages10
JournalChinese journal of cancer
Volume34
Issue number12
DOIs
Publication statusPublished - 16 Dec 2015

Cite this

Feng, Fu-Tuo ; Cui, Qian ; Liu, Wen-Sheng ; Guo, Yun-Miao ; Feng, Qi-Sheng ; Chen, Li-Zhen ; Xu, Miao ; Luo, Bing ; Li, Da-Jiang ; Hu, Li-Fu ; Middeldorp, Jaap M ; Ramayanti, Octavia ; Tao, Qian ; Cao, Su-Mei ; Jia, Wei-Hua ; Bei, Jin-Xin ; Zeng, Yi-Xin. / A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma. In: Chinese journal of cancer. 2015 ; Vol. 34, No. 12. pp. 563-72.
@article{6b26022a262e40538efae32919ac6553,
title = "A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma",
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.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.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.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.",
keywords = "Adult, Aged, Carcinoma, Case-Control Studies, China, Epstein-Barr Virus Infections, Female, Genetic Association Studies, Genome, Viral, Herpesvirus 4, Human, Humans, Incidence, Male, Middle Aged, Nasopharyngeal Neoplasms, Neoplasm Proteins, Pilot Projects, Polymorphism, Single Nucleotide, Risk Assessment, Tumor Cells, Cultured, Viral Proteins, Journal Article, Research Support, Non-U.S. Gov't",
author = "Fu-Tuo Feng and Qian Cui and Wen-Sheng Liu and Yun-Miao Guo and Qi-Sheng Feng and Li-Zhen Chen and Miao Xu and Bing Luo and Da-Jiang Li and Li-Fu Hu and Middeldorp, {Jaap M} and Octavia Ramayanti and Qian Tao and Su-Mei Cao and Wei-Hua Jia and Jin-Xin Bei and Yi-Xin Zeng",
year = "2015",
month = "12",
day = "16",
doi = "10.1186/s40880-015-0073-z",
language = "English",
volume = "34",
pages = "563--72",
journal = "Chinese journal of cancer",
issn = "1000-467X",
publisher = "Landes Bioscience",
number = "12",

}

Feng, F-T, Cui, Q, Liu, W-S, Guo, Y-M, Feng, Q-S, Chen, L-Z, Xu, M, Luo, B, Li, D-J, Hu, L-F, Middeldorp, JM, Ramayanti, O, Tao, Q, Cao, S-M, Jia, W-H, Bei, J-X & Zeng, Y-X 2015, 'A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma' Chinese journal of cancer, vol. 34, no. 12, 61, pp. 563-72. https://doi.org/10.1186/s40880-015-0073-z

A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma. / Feng, Fu-Tuo; Cui, Qian; Liu, Wen-Sheng; Guo, Yun-Miao; Feng, Qi-Sheng; Chen, Li-Zhen; Xu, Miao; Luo, Bing; Li, Da-Jiang; Hu, Li-Fu; Middeldorp, Jaap M; Ramayanti, Octavia; Tao, Qian; Cao, Su-Mei; Jia, Wei-Hua; Bei, Jin-Xin; Zeng, Yi-Xin.

In: Chinese journal of cancer, Vol. 34, No. 12, 61, 16.12.2015, p. 563-72.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma

AU - Feng, Fu-Tuo

AU - Cui, Qian

AU - Liu, Wen-Sheng

AU - Guo, Yun-Miao

AU - Feng, Qi-Sheng

AU - Chen, Li-Zhen

AU - Xu, Miao

AU - Luo, Bing

AU - Li, Da-Jiang

AU - Hu, Li-Fu

AU - Middeldorp, Jaap M

AU - Ramayanti, Octavia

AU - Tao, Qian

AU - Cao, Su-Mei

AU - Jia, Wei-Hua

AU - Bei, Jin-Xin

AU - Zeng, Yi-Xin

PY - 2015/12/16

Y1 - 2015/12/16

N2 - 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.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.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.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.

AB - 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.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.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.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.

KW - Adult

KW - Aged

KW - Carcinoma

KW - Case-Control Studies

KW - China

KW - Epstein-Barr Virus Infections

KW - Female

KW - Genetic Association Studies

KW - Genome, Viral

KW - Herpesvirus 4, Human

KW - Humans

KW - Incidence

KW - Male

KW - Middle Aged

KW - Nasopharyngeal Neoplasms

KW - Neoplasm Proteins

KW - Pilot Projects

KW - Polymorphism, Single Nucleotide

KW - Risk Assessment

KW - Tumor Cells, Cultured

KW - Viral Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1186/s40880-015-0073-z

DO - 10.1186/s40880-015-0073-z

M3 - Article

VL - 34

SP - 563

EP - 572

JO - Chinese journal of cancer

JF - Chinese journal of cancer

SN - 1000-467X

IS - 12

M1 - 61

ER -