Association between Epstein-Barr virus infection and gastric cancer: a systematic review and meta-analysis

Abstract

Background: Numerous studies conducted over the past 30 years have pointed to the presence of Epstein-Barr virus (EBV) in gastric cancer samples. This study was aimed to provide a meta-analytic review of the prevalence of EBV in gastric cancer patients, and to clarify the relationship between EBV infection and gastric cancer. Methods: A literature search was performed electronically using online databases for English language publications until July 1, 2019. The pooled EBV prevalence and 95% confidence intervals (CIs) were estimated using a randomeffects model. To determine the association between EBV and gastric cancer, pooled odds ratio (OR) and its 95% CI were computed for case-control studies. Two separate analyses were performed on data from case-control studies with matched and non-match pairs designs to calculate the pooled estimates of ORs. Results: The pooled prevalence of EBV in 20,361 gastric cancer patients was 8.77% (95% CI: 7.73-9.92%; I 2 = 83.2%). There were 20 studies with matched pairs design, including tumor and tumor-adjacent normal tissue pairs from 4116 gastric cancer patients. The pooled ORs were 18.56 (95% CI: 15.68-21.97; I 2 = 55.4%) for studies with matched pairs design and 3.31 (95% CI: 0.95-11.54; I 2 = 55.0%) for studies with non-matched pairs design. The proportion of EBV-associated gastric cancer among male cases was significantly higher than among female cases (10.83%, vs. 5.72%) (P < 0.0001). However, the pooled OR estimate for EBV-associated gastric cancer was significantly higher among females (21.47; 95% CI: 15.55-29.63; I 2 = 0%) than in males (14.07; 95% CI: 10.46-18.93; I 2 = 49.0%) (P = 0.06). EBV was more prevalent in the cardia (12.47%) and the body (11.68%) compared to the antrum (6.29%) (P = 0.0002). Conclusions: EBV infection is associated with more than 18 times increase the risk of gastric cancer. Although the prevalence of EBV was higher in male patients than in female patients with gastric cancer, women are more likely than men to develop EBV-associated gastric cancer. Our findings showed that using tumor-adjacent normal tissues as the control group provides more robust and accurate results regarding the relationship between EBV infection and gastric cancer.

Gastric cancer: Epidemiology, risk factors and prevention strategies

“…EBV infection is associated with more than 18 times increase in the risk of GC. Although the prevalence of EBV was higher in male patients than in female patients with GC, compared with males, females are more likely to develop EBV-associated GC ( 49 ). EBV-induced hypermethylation silences key tumor suppressor genes, cell cycle genes, and cellular differentiation factors to promote a highly proliferative and poorly differentiated cell population ( 50 ).…”

Immunotherapy Predictive Molecular Markers in Advanced Gastroesophageal Cancer: MSI and Beyond

“…EBV is a human herpesvirus associated with multiple cancer types such as lymphomas, nasopharyngeal carcinomas, and gastric adenocarcinomas. [ 55 , 56 ] Although the carcinogenesis role of EBV is not fully understood, gastric cancers that are positive for this virus show intense intra- and peritumoral immune cell infiltration, also higher levels of PD-L1 expression, making these tumors potentially more responsive to immune checkpoint blockade Figure 1 [ 9 , 57 ]. In a case report, a patient with EBV-positive gastric cancer had a substantial benefit from avelumab [ 58 ].…”

Wirus Epsteina-Barr w wybranych chorobach nowotworowych

“…Dobrym przykładem w przypadku EBV powiązanego z nowotworami mogą być tutaj członkowie rodziny BART miRNA przyspieszający kancerogenezę poprzez celowanie w geny wirusa lub komórki gospodarza [27]. Pomimo wielu postępów mechanizmy nowotworu żołądka powiązanego z EBV ciągle nie zostały w pełni wyjaśnione [28].…”