Nerea Fernández de Larrea-Baz1, Beatriz Pérez-Gómez2, Angelika Michel3, Beatriz Romero4, Virginia Lope2, Michael Pawlita3, Tania Fernández-Villa5, Victor Moreno6, Vicente Martín7, Martina Willhauck-Fleckenstein3, Gonzalo López-Abente2, Jesús Castilla8, Guillermo Fernández-Tardón9, Trinidad Dierssen-Sotos10, Miguel Santibáñez11, Rosana Peiró12, José Juan Jiménez-Moleón13, Carmen Navarro14, Gemma Castaño-Vinyals15, Manolis Kogevinas15, Marina Pollán2, Silvia de Sanjosé16, Rosa Del Campo17, Tim Waterboer3, Nuria Aragonés2. 1. Environmental and Cancer Epidemiology Area, National Center of Epidemiology, Carlos III Health Institute (ISCIII), Avda. Monforte de Lemos 5, 28029, Madrid, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. Electronic address: nfernandez@externos.isciii.es. 2. Environmental and Cancer Epidemiology Area, National Center of Epidemiology, Carlos III Health Institute (ISCIII), Avda. Monforte de Lemos 5, 28029, Madrid, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. 3. Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. 4. Department of Microbiology, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)-Ramón y Cajal Health Research Institute (IRYCIS), Ctra. de Colmenar Viejo km. 9,100, 28034, Madrid, Spain. 5. The Research Group in Gene - Environment and Health Interactions (GIIGAS), University of León, Spain; Department of Biomedical Sciences, Area of Preventive Medicine and Public Health, University of León, Campus de Vegazana s/n, 24071, León, Spain. 6. Cancer Prevention and Control Program, Catalan Institute of Oncology, Avinguda de la Granvia de l'Hospitalet 199-203, 08908, 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; Colorectal Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), Gran Via de l'Hospitalet, 199, 08908, Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. 7. The Research Group in Gene - Environment and Health Interactions (GIIGAS), University of León, Spain; Department of Biomedical Sciences, Area of Preventive Medicine and Public Health, University of León, Campus de Vegazana s/n, 24071, León, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. 8. Instituto de Salud Pública de Navarra, IdiSNA-Navarra Institute for Health Research, C/Leyre, 15, 31003, Pamplona, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. 9. University Institute of Oncology (IUOPA), University of Oviedo, Fernando Bongera. Building "Santiago Gascón", 1 st Floor, Campus of "El Cristo" B, 33006, Oviedo, Asturias, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. 10. University of Cantabria - IDIVAL-Instituto de Investigación Marqués de Valdecilla-Marqués de Valdecilla Research Institute (IDIVAL), C/Cardenal Herrera Oria, s/n, 39011, Santander, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. 11. University of Cantabria - IDIVAL-Instituto de Investigación Marqués de Valdecilla-Marqués de Valdecilla Research Institute (IDIVAL), C/Cardenal Herrera Oria, s/n, 39011, Santander, Spain; Centro de Investigación en Recursos Naturales, Salud, y Medio Ambiente (RENSMA), University of Huelva, Campus de El Carmen, 21007, Huelva, Spain. 12. Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana FISABIO-Salud Pública - Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), Avda. de Catalunya, 21, 46020, Valencia, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. 13. Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA)-Granada Health Research Institute (ibs.GRANADA), 18012, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Avda. de la Investigación, 11, Building A, 8th Floor, 18016, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. 14. Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Ronda de Levante, 11, 2ª planta, 30008, Murcia, Spain; Department of Health and Social Sciences, University of Murcia, Avda. Teniente Flomesta, 5, 30003, Murcia, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. 15. ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Doctor Aiguader, 88, 08003, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader, 88, 08003, Barcelona, Spain; Pompeu Fabra University (UPF), Plaça de la Mercè, 10-12, 08002, Barcelona, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. 16. Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, Avinguda de la Granvia de l'Hospitalet 199-203, 08908, l'Hospitalet de Llobregat, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)-CIBER of Epidemiology and Public Health (CIBERESP), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain. 17. Department of Microbiology, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)-Ramón y Cajal Health Research Institute (IRYCIS), Ctra. de Colmenar Viejo km. 9,100, 28034, Madrid, Spain; Red Española de Investigación en Patología Infecciosa (REIPI)-Spanish Network for Research in Infectious Diseases (REIPI), Spain.
Abstract
BACKGROUND: Helicobacter pylori infection is one of the main risk factors for non-cardia gastric cancer. However, only a minority of infected persons develop the disease. This study aims at identifying H. pylori related serological biomarkers of risk for gastric cancer. METHODS: Incident gastric cancer cases and population controls (age, sex and region frequency-matched) from the MCC-Spain multicase-control Study were included. Seroreactivities against 16H. pylori proteins were determined using multiplex serology. Infection was defined as seropositivity against≥4 proteins. Relation of serological results to non-cardia and cardia gastric cancer was assessed using multivariable mixed logistic regression and principal components analysis. RESULTS: Seroprevalence was 88% among 2071 controls, 95% among 202 non-cardia gastric cancer cases (OR=1.9 (95% CI: 1.0-3.6)) and 85% among 62 cardia cancer cases (OR=0.5 (95% CI: 0.3-1.1)). In infected subjects, seropositivity for UreA, HP231, NapA and Cagδ was associated with lower non-cardia gastric cancer risk, while seropositivity for CagA and VacA was associated with higher risk. Seropositivity for CagA and seronegativity for Cagδ maintained the association after additional adjustment by serostatus of significant proteins. We identified two antibody reactivity patterns: the "virulent-pattern", related to a threefold higher risk of non-cardia gastric cancer and the "non-virulent pattern", related to a 60% decreased risk (4th vs. first quartile). CONCLUSIONS: In our population, people seropositive for H. pylori were characterized by two patterns of antibody reactivity against H. pylori proteins: 1) Combined high seroreactivity against several proteins, associated with a lower non-cardia gastric cancer risk, and 2) High seroreactivity against CagA and VacA, associated with an increased risk.
BACKGROUND:Helicobacter pylori infection is one of the main risk factors for non-cardia gastric cancer. However, only a minority of infected persons develop the disease. This study aims at identifying H. pylori related serological biomarkers of risk for gastric cancer. METHODS: Incident gastric cancer cases and population controls (age, sex and region frequency-matched) from the MCC-Spain multicase-control Study were included. Seroreactivities against 16H. pylori proteins were determined using multiplex serology. Infection was defined as seropositivity against≥4 proteins. Relation of serological results to non-cardia and cardia gastric cancer was assessed using multivariable mixed logistic regression and principal components analysis. RESULTS: Seroprevalence was 88% among 2071 controls, 95% among 202 non-cardia gastric cancer cases (OR=1.9 (95% CI: 1.0-3.6)) and 85% among 62 cardia cancer cases (OR=0.5 (95% CI: 0.3-1.1)). In infected subjects, seropositivity for UreA, HP231, NapA and Cagδ was associated with lower non-cardia gastric cancer risk, while seropositivity for CagA and VacA was associated with higher risk. Seropositivity for CagA and seronegativity for Cagδ maintained the association after additional adjustment by serostatus of significant proteins. We identified two antibody reactivity patterns: the "virulent-pattern", related to a threefold higher risk of non-cardia gastric cancer and the "non-virulent pattern", related to a 60% decreased risk (4th vs. first quartile). CONCLUSIONS: In our population, people seropositive for H. pylori were characterized by two patterns of antibody reactivity against H. pylori proteins: 1) Combined high seroreactivity against several proteins, associated with a lower non-cardia gastric cancer risk, and 2) High seroreactivity against CagA and VacA, associated with an increased risk.
Authors: Meira Epplein; Wei-Cheng You; Julia Butt; Yang Zhang; Laura H Hendrix; Christian C Abnet; Gwen Murphy; Wei Zheng; Xiao-Ou Shu; Shoichiro Tsugane; You-Lin Qiao; Philip R Taylor; Taichi Shimazu; Keun-Young Yoo; Sue K Park; Jeongseon Kim; Sun Ha Jee; Tim Waterboer; Michael Pawlita; Kai-Feng Pan Journal: Cancer Epidemiol Biomarkers Prev Date: 2018-08-29 Impact factor: 4.254
Authors: K Muhsen; R Sinnereich; G Beer-Davidson; H Nassar; W Abu Ahmed; D Cohen; J D Kark Journal: Epidemiol Infect Date: 2019-09-25 Impact factor: 2.451