The Epstein-Barr virus latent membrane protein-1 (LMP1) 30-bp deletion and XhoI-polymorphism in nasopharyngeal carcinoma: a meta-analysis of observational studies.
BACKGROUND
Epstein-Barr virus (EBV) is considered to be closely associated with nasopharyngeal carcinoma (NPC), in which EBV-encoded latent membrane protein 1 (LMP1) was found to have an oncogenic role. However, the results published on the LMP1 polymorphism are inconsistent. In the present study, we performed a meta-analysis to determine the frequency of the associations and a more precise association between NPC and EBV LMP1 gene variants (30-bp deletion (del)/XhoI-loss).


METHODS
Eligible articles met the inclusion/exclusion criteria and were identified in the following electronic databases: PubMed, ScienceDirect, and SciELO. Consequently, the data of interest were extracted and plotted in a table to calculate the frequency and odds ratio (OR) of the outcomes of interest (30-bp del-LMP1/XhoI-loss) in patients with NPC. Study quality (Newcastle-Ottawa Scale (NOS)), publication bias, and heterogeneity were assessed.


RESULTS
Thirty-one observational studies were included with a total of 2,846 individuals (NPC, n = 1,855; control, n = 991). The risk of bias in relation to study quality evaluated by NOS was considered low. The pooled estimate of the frequency of 30-bp del-LMP1 and XhoI-loss in patients with NPC was 77% (95% confidence interval (CI): 72 to 82) and 82% (95% CI: 71 to 92), respectively. There was an association between 30-bp del-LMP1 and NPC susceptibility (OR = 2.86, 95% CI: 1.35 to 6.07, P = 0.00). Similarly, there was an association between XhoI-loss and NPC (OR = 8.5, 95% CI: 1.7 to 41, P = 0.00). However, when we analyze the co-existence of the 30-bp del-LMP1 and XhoI-loss in patients with NPC, there was no association (OR = 1.09, 95% CI: 0.06 to 18.79, P = 0.002).


CONCLUSIONS
Our results suggest an association between the 30-bp del-LMP1 and XhoI-loss with NPC susceptibility. However, our data should be interpreted with caution because the sample size was small, and there was heterogeneity between the studies. Thus, future studies are needed with adjusted estimates to simultaneously evaluate multiple factors involved in the development of NPC.


BACKGROUND
PROSPERO CRD42014013496 .
Post-Graduation Program in Applied Health Sciences, Federal University of Goiás, BR 364, Km 192, Industrial Park, Jataí, Brazil. vivbiom@gmail.com.|Virology Laboratory, Federal University of Goiás, BR 364, Km 192, Industrial Park, Jataí, Brazil. vivbiom@gmail.com.
Vivaldo G
VG
da Costa
Virology Laboratory, Federal University of Goiás, BR 364, Km 192, Industrial Park, Jataí, Brazil. ariany_marques@hotmail.com.
Ariany C
AC
Marques-Silva
Post-Graduation Program in Applied Health Sciences, Federal University of Goiás, BR 364, Km 192, Industrial Park, Jataí, Brazil. mlmoreli@jatai.ufg.br.|Virology Laboratory, Federal University of Goiás, BR 364, Km 192, Industrial Park, Jataí, Brazil. mlmoreli@jatai.ufg.br.
Marcos L
ML
Moreli
D000328:Adult; D002277:Carcinoma; D004279:DNA, Viral; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000821:virology*; D011110:Polymorphism, Genetic; D014763:Viral Matrix Proteins / Q000235:genetics*
D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008565:Membrane Proteins; D014763:Viral Matrix Proteins