Abstract 277: Multiplex Epstein-Barr virus (EBV) serology in EBV-positive and -negative gastric cancer
Authors: Camargo M. Constanza , Michel Angelika , Kim Kyoung-Mee , Matsuo Keitaro , Liao Linda M. , Torres Javier , Zabaleta Jovanny , Gulley Margaret L. , Yatabe Yasushi , Alvarado-Cabrero Isabel , Lissowska Jolanta , Kim Sung , Pawlita Michael , Rabkin Charles S. 
Published: May 2015

Abstract
BACKGROUND: The leading cause of gastric cancer is chronic Helicobacter pylori infection. However, about 10% of these tumors also contain monoclonal Epstein-Barr virus (EBV), associated with clinicopathologic differences from EBV-negative tumors. While the vast majority of the world's population is latently infected with EBV, viral reactivation is postulated to predispose to development of EBV-related tumors. To evaluate the association of EBV reactivation with EBV-positive gastric cancer, we compared anti-viral antibody profiles in subjects with EBV-positive and -negative gastric cancer using pretreatment serum samples from the U.S. National Cancer Institute's International EBV-Gastric Cancer Consortium.
METHODS: This study included 54 EBV-positive and 90 EBV-negative gastric cancer cases. A multiplex serology assay based on fluorescent polystyrene bead technology was used to measure IgG antibodies to four EBV proteins expressed in lytic and/or latent infection: BamH1 Z EBV Replication Activator (ZEBRA), early antigen D (EAD), viral capsid p18 (VCAp18) and nuclear antigen 1 (EBNA1). To account for within-population clustering, multi-level logistic regression models were used to estimate odds ratios (OR) adjusted for distributions of sex (76% male), age (mean 57 years), anatomic subsite (14% cardia, 66% noncardia, and 20% overlapping or unspecified) and year of diagnosis (1994-2013).
RESULTS: Antibody titers against ZEBRA and EAD were significantly associated with EBV-positive gastric cancer in unadjusted analyses. We found significantly elevated ORs for higher antibody titers against ZEBRA (9.9 for tertile 2 and 15 for tertile 3 vs. tertile 1; p-trend &lt;0.001) and EAD (2.3 for tertile 2 and 12 for tertile 3; p-trend &lt;0.001) in patients with EBV-positive tumors as compared to EBV-negative cases, adjusted for the possible confounders. Distribution of antibody titers against VCAp18 and EBNA1 were similar among tumor groups.
CONCLUSIONS: These data indicate viral reactivation in patients with EBV-positive gastric cancer, supporting the hypothesis that EBV infection may contribute to cancer development. Our results further implicate the virus as a co-factor in gastric carcinogenesis, and may provide a useful diagnostic marker.
Citation Format: M. Constanza Camargo, Angelika Michel, Kyoung-Mee Kim, Keitaro Matsuo, Linda M. Liao, Javier Torres, Jovanny Zabaleta, Margaret L. Gulley, Yasushi Yatabe, Isabel Alvarado-Cabrero, Jolanta Lissowska, Sung Kim, Michael Pawlita, Charles S. Rabkin. Multiplex Epstein-Barr virus (EBV) serology in EBV-positive and -negative gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 277. doi:10.1158/1538-7445.AM2014-277