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Front Microbiol. 2017 May 29;8:888. doi: 10.3389/fmicb.2017.00888. eCollection 2017.

Helicobacter pylori Antibody Reactivities and Colorectal Cancer Risk in a Case-control Study in Spain.

Author information

Environmental and Cancer Epidemiology Area, National Center of Epidemiology, Instituto de Salud Carlos IIIMadrid, Spain.
Consortium for Biomedical Research in Epidemiology and Public Health (CIBER of Epidemiology and Public Health) - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Madrid, Spain.
Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ)Heidelberg, Germany.
Department of Microbiology, Ramón y Cajal University Hospital (IRYCIS)Madrid, Spain.
Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (Puerta de Hierro Health Research Institute)Madrid, Spain.
Cancer Prevention and Control Program, Catalan Institute of OncologyHospitalet de Llobregat, Spain.
Department of Clinical Sciences, Faculty of Medicine, University of BarcelonaBarcelona, Spain.
Colorectal Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL)Hospitalet de Llobregat, Spain.
The Research Group in Gene - Environment and Health Interactions, University of LeónLeón, Spain.
Area of Preventive Medicine and Public Health, Faculty of Health Sciences, Department of Biomedical Sciences, University of LeónLeón, Spain.
Division of Epidemiology and Computational Biology, School of Medicine, University of Cantabria-IDIVALSantander, Spain.
Granada Health Research Institute (ibs.GRANADA) - Instituto de Investigación Biosanitaria de GranadaGranada, Spain.
Department of Preventive Medicine and Public Health, University of GranadaGranada, Spain.
Instituto de Salud Pública de Navarra, IdiSNA-Navarra Institute for Health ResearchPamplona, Spain.
Molecular Epidemiology of Cancer Unit, Oncology Institute, Department of Medicine, University of OviedoOviedo, Spain.
Department of Pathology, Donostia University HospitalDonostia, Spain.
Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO) - Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana FISABIO-Salud PúblicaValencia, Spain.
Coloproctology Unit, Department of General Surgery, Huelva University Hospital ComplexHuelva, Spain.
Department of Epidemiology, Regional Health Council, IMIB-ArrixacaMurcia, Spain.
Department of Health and Social Sciences, University of MurciaMurcia, Spain.
Department of Gastroenterology and Hepatology, Complejo Asistencial Universitario de LeónLeón, Spain.
Gastroenterology Department, Hospital ClínicBarcelona, Spain.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Barcelona, Spain.
CIBER Liver and Digestive Diseases - CIBER Enfermedades Hepáticas y Digestivas (CIBEREHD)Madrid, Spain.
Department of Gastroenterology, University of BarcelonaBarcelona, Spain.
ISGlobal, Centre for Research in Environmental Epidemiology (CREAL)Barcelona, Spain.
Hospital del Mar Medical Research Institute (IMIM)Barcelona, Spain.
Department of Experimental and Health Sciences, Universitat Pompeu FabraBarcelona, Spain.
Cancer Epidemiology and Research Program, Catalan Institute of Oncology-IDIBELLHospitalet de Llobregat, Spain.
Spanish Network for Research in Infectious Diseases - Red Española de Investigación en Patología InfecciosaSevilla, Spain.


Background: Several studies have suggested that Helicobacter pylori (H. pylori) infection is a risk factor for colorectal cancer (CRC), while others have not confirmed this hypothesis. This work aimed to assess the relation of CRC with H. pylori seropositivity and with seropositivity to 16 H. pylori proteins, in the MultiCase-Control study, MCC-Spain. Methods: MCC-Spain is a multicase-control study carried out in Spain from 2008 to 2013. In total, 2,140 histologically-confirmed incident CRC cases and 4,098 population-based controls were recruited. Controls were frequency-matched by sex, age, and province. Epidemiological data were collected through a questionnaire fulfilled by face-to-face interviews and a self-administered food-frequency questionnaire. Seroreactivities against 16 H. pylori proteins were determined in 1,488 cases and 2,495 controls using H. pylori multiplex serology. H. pylori seropositivity was defined as positivity to ≥4 proteins. Multivariable logistic regression mixed models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results:H. pylori seropositivity was not associated with increased CRC risk (OR = 0.91; 95% CI: 0.71-1.16). Among H. pylori seropositive subjects, seropositivity to Cagδ showed a lower CRC risk, and risk decreased with increasing number of proteins seropositive. Seropositivity to the most recognized virulence factors, CagA and VacA, was not associated with a higher CRC risk. No statistically significant heterogeneity was identified among tumor sites, although inverse relations were stronger for left colon cancer. An interaction with age and sex was found: H. pylori seropositivity was associated with a lower CRC risk in men younger than 65 and with a higher risk in older women. Conclusions: Our results suggest that neither H. pylori seropositivity, nor seropositivity to the virulence factor CagA are associated with a higher CRC risk. A possible effect modification by age and sex was identified.


Helicobacter pylori; bacterial infections; chronic infection; colorectal neoplasm; multiplex serology; non-infectious diseases

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