The Epstein-Barr virus latent membrane protein-1 (LMP1) 30-bp deletion and XhoI-polymorphism in nasopharyngeal carcinoma: a meta-analysis of observational studies

Abstract

BackgroundEpstein-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).MethodsEligible 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.ResultsThirty-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).ConclusionsOur 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.Systematic review registrationPROSPERO CRD42014013496.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-015-0037-z) contains supplementary material, which is available to authorized users.

Distribution of the Epstein‐Barr virus in the normal stomach and gastric lesions in Thai population

“…23,24 The del-LMP1 was first discovered in a NPC cell line derived from a patient in Southern China. 23 An association with this variant has been reported for several malignancies, including NPC, 17,25 but some studies have suggested that del-LMP1 is only a geographic polymorphism and is not restricted to EBV-associated malignancies. 26,27 In our study, we found del-LMP1 in eight of 43 EBV-positive cases, while the remainders were wt-LMP1.…”

Epstein–Barr virus strains and variations: Geographic or disease‐specific variants?

“…The majority of reports regarding the 30 bp-deletion of LMP1 have shown that this variation is widely spread worldwide [Hu et al, 1991;Sandvej et al, 1997;Correa et al, 2004;See et al, 2008;Tiwawech et al, 2008;Bobek et al, 2010;da Costa et al, 2015] -Table II. A recent meta-analysis, evaluated the association of this variation with NPC development and showed an association of del-LMP1 variant with NPC development described that the association is only observed in Asiatic populations while no association is observed for European and North African countries [da Costa et al, 2015]. Hence, del-LMP1 seems to be more prevalent in NPC patients than in healthy individuals and is expected to be more prevalent in NPC-endemic areas rather than non-endemic [Zhang et al, 2002;Plaza et al, 2003;Tiwawech et al, 2008;da Costa et al, 2015].…”

“…A recent meta-analysis, evaluated the association of this variation with NPC development and showed an association of del-LMP1 variant with NPC development described that the association is only observed in Asiatic populations while no association is observed for European and North African countries [da Costa et al, 2015]. Hence, del-LMP1 seems to be more prevalent in NPC patients than in healthy individuals and is expected to be more prevalent in NPC-endemic areas rather than non-endemic [Zhang et al, 2002;Plaza et al, 2003;Tiwawech et al, 2008;da Costa et al, 2015]. Similar results were found by other authors [Chang et al, 2009;Bobek et al, 2010;Banko et al, 2012;Gurtsevitch et al, 2013;Senyuta et al, 2014].…”

“…There are not many studies in healthy population, nevertheless, some studies considered XhoI restriction site only a geographic polymorphism [BenAyed‐Guerfali et al, ]. In fact, it has been described that the XhoI loss is not only associated with NPC, but especially to the Chinese race, which is corroborated by the data from the recent meta‐analysis [See et al, ; da Costa et al, ]. Moreover, there are studies in healthy individuals that refer an increased prevalence of XhoI loss in China [Zhou et al, ], while is less frequent in Western populations [Corvalan et al, ].…”

Epstein-Barr Virus and Classical Hodgkin’s Lymphoma

“…Эти мутации включали точечную мутацию, ведущую к потере сайта рестрикции XhoI в экзоне 1, и делецию 30 п.н. в карбокситерминальной области гена [43]. Было также показано, что обнаруженные мутации связаны с увеличением канцерогенности и снижением иммуноген-ности белка LMP1 [44,45].…”