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Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study
  1. Dominique S Michaud1,2,
  2. Jacques Izard3,4,
  3. Charlotte S Wilhelm-Benartzi2,5,
  4. Doo-Ho You3,
  5. Verena A Grote6,
  6. Anne Tjønneland7,
  7. Christina C Dahm8,9,
  8. Kim Overvad8,
  9. Mazda Jenab10,
  10. Veronika Fedirko10,
  11. Marie Christine Boutron-Ruault11,12,
  12. Françoise Clavel-Chapelon11,12,
  13. Antoine Racine11,12,
  14. Rudolf Kaaks6,
  15. Heiner Boeing13,
  16. Jana Foerster13,
  17. Antonia Trichopoulou14,15,
  18. Pagona Lagiou14,16,17,
  19. Dimitrios Trichopoulos16,17,
  20. Carlotta Sacerdote18,
  21. Sabina Sieri19,
  22. Domenico Palli20,
  23. Rosario Tumino21,
  24. Salvatore Panico22,
  25. Peter D Siersema23,
  26. Petra HM Peeters24,
  27. Eiliv Lund25,
  28. Aurelio Barricarte26,27,
  29. José-María Huerta27,28,
  30. Esther Molina-Montes27,29,
  31. Miren Dorronsoro30,
  32. J Ramón Quirós31,
  33. Eric J Duell32,
  34. Weimin Ye33,34,
  35. Malin Sund35,
  36. Björn Lindkvist36,
  37. Dorthe Johansen37,
  38. Kay-Tee Khaw38,
  39. Nick Wareham39,
  40. Ruth C Travis40,
  41. Paolo Vineis2,
  42. H Bas Bueno-de-Mesquita23,41,
  43. Elio Riboli2
  1. 1Department of Epidemiology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, USA
  2. 2School of Public Health, Imperial College London, London, UK
  3. 3Department of Molecular Genetics, The Forsyth Institute, Cambridge, Massachusetts, USA
  4. 4Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
  5. 5Imperial College London, London, UK
  6. 6Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  7. 7Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
  8. 8Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark
  9. 9Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
  10. 10International Agency for Research on Cancer (IARC-WHO), Lyon, France
  11. 11Inserm, Centre for Research in Epidemiology and Population Health, U1018, Institut Gustave Roussy, Villejuif, France
  12. 12Paris South University, UMRS 1018, Villejuif, France
  13. 13Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
  14. 14WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece
  15. 15Hellenic Health Foundation, Athens, Greece
  16. 16Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
  17. 17Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece
  18. 18Center for Cancer Prevention (CPO-Piemonte) and Human Genetic Foundation (HuGeF), Torino, Italy
  19. 19Nutritional Epidemiology Unit, Department of Preventive & Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  20. 20Molecular and Nutritional Epidemiology Unit, ISPO- Cancer Research and Prevention Institute, Florence, Italy
  21. 21Cancer Registry and Histopathology Unit, ‘Civile—M.P.Arezzo’ Hospital, Ragusa, Italy
  22. 22Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
  23. 23Department of Gastroenterology and Hepatology, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands
  24. 24Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands
  25. 25Institute of Community Medicine, University of Tromsø, Tromsø, Norway
  26. 26Public Health Institute of Navarra, Pamplona, Spain
  27. 27CIBER Epidemiología y Salud Pública (CIBERESP), Pamplona, Spain
  28. 28Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain
  29. 29Andalusian School of Public Health, Granada, Spain
  30. 30Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain
  31. 31Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain
  32. 32Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
  33. 33Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  34. 34The Medical Biobank at Umeå University, Umeå, Sweden
  35. 35Departments of Surgical and Perioperative Sciences, Surgery and Public Health and Clinical Medicine, Nutrition Research, Umeå University, Umeå, Sweden
  36. 36Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  37. 37Department of Surgery, Skåne University Hospital, SUS, Malmö, Sweden
  38. 38School of Clinical Medicine, University of Cambridge, Cambridge, UK
  39. 39MRC Epidemiology Unit, Cambridge, UK
  40. 40Nuffield Department of Clinical Medicine, Cancer Epidemiology Unit, University of Oxford, Oxford, UK
  41. 41National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
  1. Correspondence toDr Dominique S Michaud, Department of Epidemiology, Brown University, Box G-S121-2, Providence, RI 02912, USA;Dominique_Michaud{at}


Objective Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study.

Design We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study. Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index.

Results Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a twofold higher risk of pancreatic cancer than individuals with lower levels of these antibodies (OR 2.14; 95% CI 1.05 to 4.36; >200 ng/ml vs ≤200 ng/ml). To explore the association with commensal (non-pathogenic) oral bacteria, we performed a cluster analysis and identified two groups of individuals, based on their antibody profiles. A cluster with overall higher levels of antibodies had a 45% lower risk of pancreatic cancer than a cluster with overall lower levels of antibodies (OR 0.55; 95% CI 0.36 to 0.83).

Conclusions Periodontal disease might increase the risk for pancreatic cancer. Moreover, increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer. Studies are needed to determine whether oral bacteria have direct effects on pancreatic cancer pathogenesis or serve as markers of the immune response.

  • Pancreatic Cancer
  • Epidemiology
  • Bacterial Pathogenesis

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