Epstein-Barr virus and risk of non-Hodgkin lymphoma in the cancer prevention study-II and a meta-analysis of serologic studies
INTERNATIONAL JOURNAL OF CANCER
Authors: Teras, Lauren R.; Rollison, Dana E.; Pawlita, Michael; Michel, Angelika; Brozy, Johannes; de Sanjose, Silvia; Blase, Jennifer L.; Gapstur, Susan M.
Abstract
Epstein-Barr virus (EBV) causes rare, malignant lymphomas. The role of EBV in other non-Hodgkin lymphomas (NHLs) remains unclear, but mildly reduced immune function could lead to reactivation of EBV and subsequent NHL. We examined the association between prospectively-collected plasma EBV antibodies and NHL risk in the Cancer Prevention Study-II (CPS-II) Nutrition Cohort and conducted a meta-analysis of our and published results. The CPS-II study included 225 NHL cases and 2:1 matched controls. No associations were observed between EBV serostatus or antibody levels and risk of NHL overall. However, when including only the three most common types of NHL (diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma), high compared to low early antigen (EA-D) diffuse and BZLF1-encoded replication activator antibodies were associated with approximately 60% higher risk of NHL. Odds ratios (ORs) for EBV nuclear antigen-1 and viral capsid antigen (VCA)-p18 were elevated but not statistically significant. In the meta-analysis, both EA (summary OR = 1.52, 95% confidence interval (CI): 1.16-2.00) and VCA (summary OR = 1.20, 95% CI: 1.00-1.44) were positively associated with NHL risk. These results suggest EBV may be associated with a wider spectrum of NHL subtypes, but further study is needed to confirm and fully understand these associations.
Clinical values of multiple Epstein-Barr virus (EBV) serological biomarkers detected by xMAP technology
JOURNAL OF TRANSLATIONAL MEDICINE
Authors: Gu, Ai-Di; Lu, Li-Xia; Xie, Yan-Bo; Chen, Li-Zhen; Feng, Qi-Sheng; Kang, Tiebang; Jia, Wei-Hua; Zeng, Yi-Xin
Abstract
Background: Serological examination of Epstein-Barr virus (EBV) antibodies has been performed for screening nasopharyngeal carcinoma (NPC) and other EBV-associated diseases. Methods: By using xMAP technology, we examined immunoglobulin (Ig) A antibodies against Epstein-Barr virus ( EBV) VCA-gp125, p18 and IgA/IgG against EA-D, EBNA1 and gp78 in populations with distinct diseases, or with different genetic or geographic background. Sera from Cantonese NPC patients (n = 547) and healthy controls (n = 542), 90 members of high-risk NPC families and 52 non-endemic healthy individuals were tested. Thirty-five of NPC patients were recruited to observe the kinetics of EBV antibody levels during and after treatment. Patients with other EBV-associated diseases were collected, including 16 with infectious mononucleosis, 28 with nasal NK/T cell lymphoma and 14 with Hodgkin's disease. Results: Both the sensitivity and specificity of each marker for NPC diagnosis ranged 61-84%, but if combined, they could reach to 84.5% and 92.4%, respectively. Almost half of NPC patients displayed decreased EBV immunoactivities shortly after therapy and tumor recurrence was accompanied with high EBV antibody reactivates. Neither the unaffected members from high-risk NPC families nor non-endemic healthy population showed statistically different EBV antibody levels compared with endemic controls. Moreover, elevated levels of specific antibodies were observed in other EBV-associated diseases, but all were lower than those in NPC. Conclusion: Combined EBV serological biomarkers could improve the diagnostic values for NPC. Diverse EBV serological spectrums presented in populations with different EBV-associated diseases, but NPC patients have the highest EBV activity.