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Antibody Responses to Helicobacter pylori and Risk of Developing Colorectal Cancer in a European Cohort

Butt J 1 , Jenab M 2 , Pawlita M 1 , Tjønneland A 3 , Kyrø C 3 , Boutron-Ruault MC 4 Show all authors , Carbonnel F 4 , Dong C 4 , Kaaks R 5 , Kühn T 5 , Boeing H 6 , Schulze MB 7 , Trichopoulou A 8 , Karakatsani A 8 , La Vecchia C 8 , Palli D 9 , Agnoli C 10 , Tumino R 11 , Sacerdote C 12 , Panico S 13 , Bueno-de-Mesquita B 14 , Vermeulen R 15 , Gram IT 16 , Weiderpass E 2 , Borch KB 16 , Quirós JR 17 , Agudo A 18 , Rodríguez-Barranco M 19 , Santiuste C 19 , Ardanaz E 19 , Van Guelpen B 20 , Harlid S 20 , Imaz L 21 , Perez-Cornago A 22 , Gunter MJ 2 , Zouiouich S 2 , Park JY 2 , Riboli E 23 , Cross AJ 23 , Heath AK 23 , Waterboer T 1 , Hughes DJ 24

Affiliations 

  • 1 Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 2 International Agency for Research on Cancer (IARC-WHO), Lyon, France
  • 3 Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
  • 4 CESP, Faculté de Médecine, Université Paris-Sud and Faculté de Médecine, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France
  • 5 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 6 Department of Epidemiology, German Institute of Human Nutrition Potsdam, Rehbruecke, Nuthetal, Germany
  • 7 Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam, Rehbruecke, Nuthetal, Germany
  • 8 Hellenic Health Foundation, Athens, Greece
  • 9 Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network-ISPRO, Florence, Italy
  • 10 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • 11 Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy
  • 12 Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy
  • 13 Dipartimento die Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
  • 14 Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands
  • 15 Julius Center for Health Sciences and Primary Care, Cancer Epidemiology, University Medical Center Utrecht, the Netherlands
  • 16 Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
  • 17 Public Health Directorate, Asturias, Spain
  • 18 Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Barcelona, Spain
  • 19 CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
  • 20 Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
  • 21 Ministry of Health of the Basque Government, Public Health Division of Gipuzkoa, Donostia-San Sebastian, Spain
  • 22 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
  • 23 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
  • 24 Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland. [email protected]
Cancer Epidemiol Biomarkers Prev, 2020 Jul;29(7):1475-1481.
PMID: 32332031 DOI: 10.1158/1055-9965.EPI-19-1545

Abstract

BACKGROUND: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer development. However, prospective studies addressing H. pylori and colorectal cancer are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

METHODS: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific seropositivity with odds of developing colorectal cancer.

RESULTS: Fifty-one percent of colorectal cancer cases were H. pylori seropositive compared with 44% of controls, resulting in an OR of 1.36 (95% CI, 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by seropositivity to Helicobacter cysteine-rich protein C (HcpC; OR: 1.66; 95% CI, 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34; 95% CI, 0.99-1.82), the latter being nonstatistically significant only in the fully adjusted model.

CONCLUSIONS: In this prospective multicenter European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing colorectal cancer.

IMPACT: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease colorectal cancer incidence.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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