Nasopharyngeal carcinoma patients from Norway show elevated Epstein-Barr virus IgA and IgG antibodies prior to diagnosis |
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| Affiliation: | 1. Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany;2. Department of Research, Cancer Registry of Norway, Oslo, Norway;3. Department of Epidemiology and Biostatistics, Imperial College London, London, UK;4. Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway;5. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA;6. Cancer Registry of Norway, Oslo, Norway;7. Genetic Epidemiology Group (GEP), International Agency for Research on Cancer (IARC), Lyon, France;8. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA;9. University of Bristol Dental School and University Hospitals Bristol and Weston NHS Foundation Trust Bristol, UK;1. Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen, Denmark;2. Statistics and Data Analysis, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen, Denmark;3. Department of Gynecology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen, Denmark;1. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA;2. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA;3. Division of Preventive Medicine, Brigham and Women''s Hospital and Harvard Medical School, Boston, MA, USA;4. Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA;5. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA;6. Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;7. Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;8. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA;9. Department of Global Health, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA;10. Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA;1. Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran;2. Golestan Research Centre of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran;3. Department of Public Health, Golestan University of Medical Sciences, Gorgan, Iran;4. Deputy of Treatment, Golestan University of Medical Sciences, Gorgan, Iran;5. Deputy of Health, Ministry of Health and Medical Education, Iran;6. Cancer Surveillance Branch, International Agency for Research on Cancer, France;1. Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan;2. Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan;1. Viral Oncology Section, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD;2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei 230000, Anhui, China;2. Laboratory for Environmental Toxicology, Anhui Medical University, Hefei 230032, Anhui, China |
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| Abstract: | BackgroundIgA antibodies against few Epstein-Barr virus (EBV) proteins are established serological markers for nasopharyngeal carcinoma (NPC). We recently validated a novel, comprehensive EBV marker panel and showed that IgA, but also IgG antibodies against multiple EBV proteins are highly sensitive and specific for EBV-positive NPC at diagnosis. However, data about these novel biomarkers as prospective markers for NPC are sparse.MethodsThis study included 30 incident NPC cases and 60 matched controls from the Norwegian Janus Serum Bank. For 21 NPCs, molecular EBV and human papillomavirus (HPV) status were assessed by EBER-ISH and HPV DNA/RNA testing by PCR, respectively. IgA and IgG serum antibodies against 17 EBV antigens were analyzed in prediagnostic sera of cases (median lead time 14 years) and controls using multiplex serology. Sensitivities were calculated using receiver operating characteristic analysis pre-specified to yield 90% specificity in the control group. From 10 cases, serial samples were available.ResultsQuantitative EBV antibody levels were significantly elevated among all cases (p < 0.05) for three IgA and six IgG antibodies. The highest sensitivities for defining 12 EBER-ISH-positive NPCs were observed for BGLF2 IgA (67%) and BGLF2 IgG (83%). Increased IgA and IgG antibody levels between the first and last draw before diagnosis were observed for EBER-ISH positive, but not for EBER-ISH negative NPCs. Among 21 molecularly analyzed NPCs, 4 EBER-ISH negative NPCs showed concomitant positivity to HPV type-specific DNA and RNA; 3 NPCs were HPV16 and 1 NPC was HPV18 positive.ConclusionBoth, EBV IgA and IgG antibody levels are significantly elevated many years before diagnosis of EBV-positive NPCs in Norway, an NPC low-incidence region. This study provides insights into one of the largest available prospective sample collections of NPCs in a non-endemic country. |
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| Keywords: | Nasopharyngeal carcinoma Epstein-Barr virus Multiplex serology Prospective biomarker Nested case/control study |
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