Epstein Barr virus antibody reactivity and gastric cancer: A population-based case-control study

Nuria Aragonés; Nerea Fernández de Larrea; Roberto Pastor-Barriuso; Angelika Michel; Beatriz Romero; Michael Pawlita; Sara Mayorgas-Torralba; Vicente Martín; Victor Moreno; Delphine Casabonne; Jesús Castilla; Guillermo Fernandez-Tardón; Trinidad Dierssen-Sotos; Rocío Capelo; Dolores Salas; Inmaculada Salcedo-Bellido; María Dolores Chirlaque; Nicole Brenner; Manuela Pedraza; Xavier Bessa; Beatriz Pérez-Gómez; Julia Butt; Manolis Kogevinas; Rosa Del Campo; Silvia de Sanjosé; Tim Waterboer; Marina Pollán

doi:10.1016/j.canep.2019.05.008

Epstein Barr virus antibody reactivity and gastric cancer: A population-based case-control study

Cancer Epidemiol. 2019 Aug:61:79-88. doi: 10.1016/j.canep.2019.05.008. Epub 2019 May 30.

Authors

Nuria Aragonés¹, Nerea Fernández de Larrea², Roberto Pastor-Barriuso³, Angelika Michel⁴, Beatriz Romero⁵, Michael Pawlita⁴, Sara Mayorgas-Torralba⁶, Vicente Martín⁷, Victor Moreno⁸, Delphine Casabonne⁹, Jesús Castilla¹⁰, Guillermo Fernandez-Tardón¹¹, Trinidad Dierssen-Sotos¹², Rocío Capelo¹³, Dolores Salas¹⁴, Inmaculada Salcedo-Bellido¹⁵, María Dolores Chirlaque¹⁶, Nicole Brenner⁴, Manuela Pedraza¹⁷, Xavier Bessa¹⁸, Beatriz Pérez-Gómez³, Julia Butt⁴, Manolis Kogevinas¹⁹, Rosa Del Campo²⁰, Silvia de Sanjosé⁹, Tim Waterboer⁴, Marina Pollán³

Affiliations

¹ Epidemiology Section, Public Health Division, Department of Health of Madrid, C/San Martín de Porres, 6, 28035, Madrid, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain.
² National Center of Epidemiology, Carlos III Health Institute, Avenida Monforte de Lemos, 5, 28029, Madrid, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. Electronic address: nfernandez@isciii.es.
³ National Center of Epidemiology, Carlos III Health Institute, Avenida Monforte de Lemos, 5, 28029, Madrid, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 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; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, 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; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Gran Via de les Corts Catalanes, 585, 08007, Barcelona, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain.
⁹ Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, Gran Via de L'Hospitalet, 199-203, 08908, L'Hospitalet de Llobregat, Barcelona, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain.
¹⁰ Instituto de Salud Pública de Navarra, IdiSNA-Navarra Institute for Health Research, C/Leyre, 15, 31003, Pamplona, Navarra, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain.
¹¹ University Institute of Oncology (IUOPA), University of Oviedo, Building "Santiago Gascón", 1st Floor. Campus of "El Cristo" B, 33006, Oviedo, Asturias, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain.
¹² 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; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain.
¹³ Natural Resources, Health and Environment Research Center (RENSMA), University of Huelva, Avenida de las Fuerzas Armadas, s/n, 21007, Huelva, Spain.
¹⁴ Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), C/Micer Mascó, 31, 46010, Valencia, Spain; General Directorate Public Health, Valencian Community, Avenida de Cataluña, 21, 46020, Valencia, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain.
¹⁵ Preventive Medicine and Public Health Department, Faculty of Medicine, University of Granada, Avenida de la Investigación, 11, 18071, Granada, Spain; Granada Health Research Institute (ibs.GRANADA). Complejo Hospitalario Universitario de Granada, Avenida de las Fuerzas Armadas, 2, 18014, Granada, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain.
¹⁶ Department of Epidemiology, Murcia Health Authority, IMIB-Arrixaca, Ronda de Levante, 11, 30008, Murcia, Spain; Department of Health and Social Sciences, University of Murcia, Avenida Teniente Flomesta, 5, 30003, Murcia, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain.
¹⁷ Department of Oncology, Complejo Asistencial Universitario de León, Altos de Nava, s/n, 24071, León, Spain.
¹⁸ Department of Gastroenterology, Hospital del Mar, Dr. Aiguader, 88, 08003, Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Dr. Aiguader, 88, 08003, Barcelona, Spain.
¹⁹ ISGlobal, Doctor Aiguader, 88, 08003, Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Dr. Aiguader, 88, 08003, Barcelona, Spain; Pompeu Fabra University (UPF), Plaça de la Mercè, 10-12, 08002, Barcelona, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain.
²⁰ 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; Spanish Network for Research in Infectious Diseases (REIPI), Avenida Dr. Fedriani, s/n, 41071, Sevilla, Spain.

PMID: 31154081
DOI: 10.1016/j.canep.2019.05.008

Abstract

Background: In 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.

Methods: We 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.

Results: Among 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.

Conclusion: Our 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.

Keywords: Causality; Epstein-Barr virus; Gastric cancer; Multiplex serology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Case-Control Studies
Epstein-Barr Virus Infections / complications*
Female
Humans
Male
Middle Aged
Risk Factors
Stomach Neoplasms / pathology
Stomach Neoplasms / virology*