Epstein Barr virus antibody reactivity and gastric cancer: A population-based case-control study |
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| Institution: | 1. Epidemiology Section, Public Health Division, Department of Health of Madrid, C/San Martín de Porres, 6, 28035, Madrid, Spain;2. CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain;3. National Center of Epidemiology, Carlos III Health Institute, Avenida Monforte de Lemos, 5, 28029, Madrid, Spain;4. Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany;5. Department of Microbiology, Hospital Universitario Ramón y Cajal and Ramón y Cajal Health Research Institute (IRYCIS), Carretera de Colmenar Viejo, km. 9,100, 28034, Madrid, Spain;6. Department of Preventive Medicine and Public Health, Hospital Universitario Rey Juan Carlos, C/Gladiolo, s/n, 28933, Móstoles, Madrid, Spain;7. The Research Group in Gene - Environment and Health Interactions (GIIGAS), Biomedicine Institute (IBIOMED), University of León, Vegazana Campus, s/n, 24071, León, Spain;8. Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), and ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Gran Via de l’Hospitalet, 199-203, 08908, L''Hospitalet de Llobregat, Barcelona, Spain;9. Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Gran Via de les Corts Catalanes, 585, 08007, Barcelona, Spain;10. Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, Gran Via de L''Hospitalet, 199-203, 08908, L’Hospitalet de Llobregat, Barcelona, Spain;11. Instituto de Salud Pública de Navarra, IdiSNA-Navarra Institute for Health Research, C/Leyre, 15, 31003, Pamplona, Navarra, Spain;12. University Institute of Oncology (IUOPA), University of Oviedo, Building \"Santiago Gascón\", 1st Floor. Campus of \"El Cristo\" B, 33006, Oviedo, Asturias, Spain;13. Department of Medical and Surgical Sciences, University of Cantabria - Marqués de Valdecilla Research Institute (IDIVAL), C/Cardenal Herrera Oria, s/n, 39011, Santander, Cantabria, Spain;14. Natural Resources, Health and Environment Research Center (RENSMA), University of Huelva, Avenida de las Fuerzas Armadas, s/n, 21007, Huelva, Spain;15. Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), C/Micer Mascó, 31, 46010, Valencia, Spain;p. General Directorate Public Health, Valencian Community, Avenida de Cataluña, 21, 46020, Valencia, Spain;q. Preventive Medicine and Public Health Department, Faculty of Medicine, University of Granada, Avenida de la Investigación, 11, 18071, Granada, Spain;r. Granada Health Research Institute (ibs.GRANADA). Complejo Hospitalario Universitario de Granada, Avenida de las Fuerzas Armadas, 2, 18014, Granada, Spain;s. Department of Epidemiology, Murcia Health Authority, IMIB-Arrixaca, Ronda de Levante, 11, 30008, Murcia, Spain;t. Department of Health and Social Sciences, University of Murcia, Avenida Teniente Flomesta, 5, 30003, Murcia, Spain;u. Department of Oncology, Complejo Asistencial Universitario de León, Altos de Nava, s/n, 24071, León, Spain;v. Department of Gastroenterology, Hospital del Mar, Dr. Aiguader, 88, 08003, Barcelona, Spain;w. Hospital del Mar Medical Research Institute (IMIM), Dr. Aiguader, 88, 08003, Barcelona, Spain;x. ISGlobal, Doctor Aiguader, 88, 08003, Barcelona, Spain;y. Pompeu Fabra University (UPF), Plaça de la Mercè, 10-12, 08002, Barcelona, Spain;z. Spanish Network for Research in Infectious Diseases (REIPI), Avenida Dr. Fedriani, s/n, 41071, Sevilla, Spain;1. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States;2. Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences Durham, NC, United States;3. Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States;4. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States;5. Biospecimen Processing Center, University of North Carolina, Chapel Hill, NC, United States;6. Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA, United States;7. Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA, United States;8. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States;9. Showers Center for Childhood Cancer and Blood Disorder, Akron Children’s Hospital, Akron, OH, United States;10. Department of Biostatistics, Colleges of Medicine and Public Health & Health Professions, University of Florida, Children’s Oncology Group Statistics & Data Center, Gainesville, FL, United States;11. Department of Otolaryngology, Washington University School of Medicine, St Louis, MO, 63110;1. Centre for Big Data Research in Health, University of New South Wales Sydney, NSW, Australia;2. Centre for Primary Health Care and Equity, University of New South Wales Sydney, NSW, Australia;3. School of Medicine, University of Wollongong, NSW, Australia;4. National Drug and Alcohol Research Centre, University of New South Wales Sydney, NSW, Australia;5. Faculty of Medicine and Health, University of Sydney, NSW, Australia;6. Cancer Voices NSW, NSW, Australia;1. Institute of Medical Epidemiology, Biostatistics and Informatics, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Germany;2. Section of Cancer Information, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France;3. Department of Medicine, University of Zimbabwe School of Medicine, Harare, Zimbabwe;4. Department of Pathology, Maputo Central Hospital, Maputo, Mozambique;5. CTSU, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7FL, United Kingdom;6. African Cancer Registry Network, 267 Banbury Road, Oxford OX2 7HT, United Kingdom;1. Moffitt Cancer Center, Department of Health Outcomes and Behavior, 4115 E. Fowler Ave., Tampa, FL 33617, United States;2. Moffitt Cancer Center, Center for Immunization and Infection Research in Cancer, 12902 USF Magnolia Drive, Tampa, FL 33612, United States;3. Moffitt Cancer Center, Department of Cancer Epidemiology, 12902 USF Magnolia Drive, Tampa, FL 33612, United States;4. Moffitt Cancer Center, Department of Biostatistics and Bioinformatics, 12902 USF Magnolia Drive, Tampa, FL 33612, United States;5. University of South Florida, Department of Family Medicine, 13330 USF Laurel Drive, Tampa, FL 33612, United States;6. University of South Florida, Department of Epidemiology & Biostatistics, 13201 Bruce B Downs Blvd, Tampa, FL 33612, United States;8. University of Florida, Department of Medicine, 1600 SW Archer Rd., Gainesville, FL 32608, United States;9. University of Florida Health, Department of Health Outcomes and Biomedical Informatics, 2004 Mowry Road, Ste 2245, Gainesville, FL 32610, United States;10. University of Florida Health, Cancer Population Sciences, 2004 Mowry Road, Ste 2245, Gainesville, FL 32610, United States;1. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;2. Department of Health and Human Performance, University of Houston, TX, USA;3. Health Disparities Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;1. Department of Medicine, University of Kentucky, Lexington, KY, United States;2. Department of Neurology, University of Kentucky, Lexington, KY, United States;3. Departments of Neurosurgery, University of Kentucky, Lexington, KY, United States;4. Departments of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, United States;5. Markey Cancer Center, University of Kentucky, Lexington, KY, United States |
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| Abstract: | BackgroundIn contrast to the recognized role of Helicobacter pylori in the etiology of non-cardia gastric cancer (GC), there is still insufficient epidemiological evidence for the involvement of Epstein-Barr virus (EBV) in gastric carcinogenesis. We aimed to evaluate the relation of antibody profile and antibody reactivity intensity against four individual EBV proteins to GC risk.MethodsWe used information from 281 GC cases and 2071 age and sex frequency matched controls recruited in the frame of the MCC-Spain multicase-control study, between 2008 and 2013. Sociodemographic, lifestyle and environmental factors were assessed in face-to-face interviews. Antibody responses to four EBV proteins (EBNA-1, ZEBRA, EA-D, and VCA-p18) were analyzed by multiplex serology. Odds ratios (OR) and 95% confidence intervals were calculated by using logistic regression mixed models to evaluate the association of seropositivity and antibody reactivity against EBV proteins with GC, adjusting for GC risk factors. Stratified analyses by tumor location (cardia vs. non-cardia) and morphology (intestinal vs. diffuse) were done.ResultsAmong controls, seropositivity for EA-D, ZEBRA, EBNA-1 and VCA-p18 was 85%, 91%, 97% and 99%, respectively. Even though seropositivity for none of the studied proteins was associated with a higher GC risk, increasing antibody reactivity against EBNA-1 and VCA-p18 was associated with higher OR of GC. This association was present for cardia and non-cardia cancer cases, and for intestinal and diffuse types.ConclusionOur results support the hypothesis that EBV may play a role in GC etiology, and highlight the importance of evaluating specific antibodies and the dose-response relations when studying widespread infections. |
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| Keywords: | Gastric cancer Epstein-Barr virus Multiplex serology Causality |
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