A Systematic Review of Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) Gene Variants in Nasopharyngeal Carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is an aggressive tumor with a complex etiology. Although Epstein-Barr virus (EBV) infection is known environmental factor for NPC development, the degree to which EBV naturally infects nasopharyngeal epithelium and the moment when and why the virus actively begins to affect cell transformation remains questionable. The aim of this study was to explore the association between LMP1 gene variability and potential contribution to NPC development. A systematic review was performed through searches of PubMed, Web of Science (WoS) and SCOPUS electronic databases. Additionally, meta-analysis of the difference in the frequency of seven LMP1 gene variants in NPC and control individuals was accomplished. The results from this study give a proof of concept for the association between 30 bp deletion (OR = 3.53, 95% CI = 1.48-8.43) and Xhol loss (OR = 14.17, 95% CI = 4.99-40.20) and NPC susceptibility when comparing biopsies from NPC and healthy individuals. Otherwise, 30 bp deletion from NPC biopsies could not distinguish NPC from EBV-associated non-NPC tumors (OR = 1.74, 95% CI = 0.81-3.75). However, B95-8, China1 and North Carolina variants were uncommon for NPC individuals. Much more efforts remains to be done to verify the biological significance of the differences observed, define so-called "high-risk" EBV variants and make it available for clinical application.

Keywords: EBV; LMP1; gene variability; meta-analysis; nasopharyngeal carcinoma; variants.

Figure 1

Flow chart.

Figure 2

Forest plot of the frequency of the occurrence of Xhol loss in biopsies from NPC and other EBV-associated tumors patients. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 3

Forest plot of the frequency of the occurrence of Xhol loss in biopsies from NPC and healthy individuals. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 4

Forest plot of the frequency of the occurrence of Xhol loss in biopsies from NPC and TWs from healthy individuals. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 5

Forest plot of the frequency of the occurrence of 30 bp del in biopsies from NPC and healthy individuals. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 6

Forest plot of the frequency of the occurrence of 30 bp del in biopsies from NPC and TWs from healthy individuals. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 7

Forest plot of the frequency of the occurrence of 30 bp del in biopsies from NPC and other EBV-associated tumors patients. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 8

Forest plot of the frequency of the occurrence of 30 bp del in TWs from NPC and healthy individuals. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 9

Forest plot of the frequency of the occurrence of 30 bp del in blood from NPC and healthy individuals. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 10

Forest plot of the frequency of the occurrence of 69 bp del in biopsies from NPC and other EBV-associated tumor patients. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 11

Forest plot of the frequency of the occurrence of 69 bp del in NPC biopsies and blood from healthy individuals. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 12

Forest plot of the frequency of the occurrence of B95-8 in blood samples from NPC and healthy individuals. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 13

Forest plot of the frequency of the occurrence of B95-8 loss in biopsies from NPC and healthy individuals. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 14

Forest plot of the frequency of the occurrence of B95-8 in TWs from NPC and healthy individuals. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 15

Forest plot of the frequency of the occurrence of China1 in biopsies from NPC and other EBV-associated tumors patients. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 16

Forest plot of the frequency of the occurrence of China1 in blood samples from NPC and other EBV-associated tumors patients. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 17

Forest plot of the frequency of the occurrence of China1 in TWs from NPC and other EBV-associated tumors patients. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 18

Forest plot of the frequency of the occurrence of Med in biopsies from NPC and other EBV-associated tumors patients. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 19

Forest plot of the frequency of the occurrence of Med in blood samples from NPC and other EBV-associated tumors patients. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 20

Forest plot of the frequency of the occurrence of Med in TWs from NPC and other EBV-associated tumors patients. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 21

Forest plot of the frequency of the occurrence of NC in biopsies from NPC and other EBV-associated tumors patients. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 22

Forest plot of the frequency of the occurrence of 30 bp del in biopsies from NPC and healthy individuals in endemic regions. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 23

Forest plot of the frequency of the occurrence of 30 bp del in NPC biopsies and TWs from healthy individuals in endemic regions. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 24

Forest plot of the frequency of the occurrence of 30 bp del in biopsies from NPC and other EBV-associated tumors patients in endemic regions. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 25

Forest plot of the frequency of the occurrence of 30 bp del in biopsies from NPC and other EBV-associated tumors patients in non-endemic regions. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 26

Forest plot of the frequency of the occurrence of Xhol loss in biopsies from NPC and other EBV-associated tumors patients in non-endemic regions. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).

Figure 27

Forest plot of the frequency of the occurrence of Xhol loss in biopsies from NPC and other EBV-associated tumors patients in endemic regions. The confidence interval (CI) was 95%, and the diamond represents the pooled estimate (The blue squares represent point estimation of each study weighted for population size).