Grant Number:	1R21CA139193-01A1 Interpret this number
Primary Investigator:	Michaud, Dominique
Organization:	Brown University
Project Title:	Serological Markers of Periodontal Disease and Pancreatic Cancer Risk
Fiscal Year:	2010

DESCRIPTION (provided by applicant): Pancreas cancer is the fourth leading cause of cancer-related death and is highly lethal; 95% of patients with this cancer die within 5 years of initial diagnosis. Understanding the etiology of pancreatic cancer is critical to implement steps towards prevention and may concurrently provide insights on how to treat and detect this malignancy. Little is known about the causes of pancreatic cancer; tobacco smoke, chronic pancreatitis, familial syndromes, and other suspected risk factors can only explain 25-30% of all pancreatic cancer cases. Several studies support an association between periodontitis and pancreatic cancer risk; in a recent publication, this association was observed among never smokers in a large prospective cohort of health professionals. The implications for this association, if confirmed, are substantial and will include the need for more efforts towards understanding the underlying mechanisms. As periodontal disease is difficult to measure in epidemiologic settings, our proposal to use antibodies to periodontal organisms should shed light on the plausibility of this association in an efficient and rapid fashion. Furthermore, our approach will avoid concerns of measurement error related to use of self-report of periodontal disease or use of retrospective assessment of periodontal disease in a case-control setting. Our study will be able to directly address the question of whether periodontal infection was present before the cancer onset as all bloods were collected pre-diagnostically. For this study, we propose to measurement antibodies to four common periodontal bacterial pathogens and to anaerobic bacteria that have been linked to pancreatitis and are also part of the oral microbiome. The association between the antibodies tested and pancreatic cancer will be examined using 468 pancreatic cancer cases and matched controls from the European Prospective Investigation into Cancer (EPIC) cohort study. Detailed data on risk factors of pancreatic cancer are available in this study and will be included in the analysis to control for potential confounding. This study should provide valuable data to further evaluate the potential role of periodontal disease in the etiology of pancreatic cancer and may provide a new area of research for the prevention of this highly fatal cancer. PUBLIC HEALTH RELEVANCE: This study will provide valuable data on periodontal disease and pancreatic cancer risk and may open a new area of research for this highly fatal cancer. In addition, findings from this study could lead to insights into the mechanism of pancreatic cancer which may translate into prevention recommendations or treatments that could reduce the incidence and mortality from this highly lethal malignancy.




Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study.
Authors: Michaud D.S. , Izard J. , Wilhelm-Benartzi C.S. , You D.H. , Grote V.A. , Tjønneland A. , Dahm C.C. , Overvad K. , Jenab M. , Fedirko V. , et al. .
Source: Gut, 2013 Dec; 62(12), p. 1764-70.
PMID: 22990306
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Lifestyle, dietary factors, and antibody levels to oral bacteria in cancer-free participants of a European cohort study.
Authors: Michaud D.S. , Izard J. , Rubin Z. , Johansson I. , Weiderpass E. , Tjønneland A. , Olsen A. , Overvad K. , Boutron-Ruault M.C. , Clavel-Chapelon F. , et al. .
Source: Cancer Causes & Control : Ccc, 2013 Nov; 24(11), p. 1901-9.
PMID: 23901020
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Role of bacterial infections in pancreatic cancer.
Authors: Michaud D.S. .
Source: Carcinogenesis, 2013 Oct; 34(10), p. 2193-7.
PMID: 23843038
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Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples.
Authors: Segata N. , Haake S.K. , Mannon P. , Lemon K.P. , Waldron L. , Gevers D. , Huttenhower C. , Izard J. .
Source: Genome Biology, 2012-06-14 00:00:00.0; 13(6), p. R42.
EPub date: 2012-06-14 00:00:00.0.
PMID: 22698087
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Structure, function and diversity of the healthy human microbiome.
Authors: Human Microbiome Project Consortium .
Source: Nature, 2012-06-13 00:00:00.0; 486(7402), p. 207-14.
EPub date: 2012-06-13 00:00:00.0.
PMID: 22699609
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A framework for human microbiome research.
Authors: Human Microbiome Project Consortium .
Source: Nature, 2012-06-13 00:00:00.0; 486(7402), p. 215-21.
EPub date: 2012-06-13 00:00:00.0.
PMID: 22699610
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Efficient and robust RNA-seq process for cultured bacteria and complex community transcriptomes.
Authors: Giannoukos G. , Ciulla D.M. , Huang K. , Haas B.J. , Izard J. , Levin J.Z. , Livny J. , Earl A.M. , Gevers D. , Ward D.V. , et al. .
Source: Genome Biology, 2012; 13(3), p. R23.
PMID: 22455878
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Metabolic reconstruction for metagenomic data and its application to the human microbiome.
Authors: Abubucker S. , Segata N. , Goll J. , Schubert A.M. , Izard J. , Cantarel B.L. , Rodriguez-Mueller B. , Zucker J. , Thiagarajan M. , Henrissat B. , et al. .
Source: Plos Computational Biology, 2012; 8(6), p. e1002358.
PMID: 22719234
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Microbial co-occurrence relationships in the human microbiome.
Authors: Faust K. , Sathirapongsasuti J.F. , Izard J. , Segata N. , Gevers D. , Raes J. , Huttenhower C. .
Source: Plos Computational Biology, 2012; 8(7), p. e1002606.
PMID: 22807668
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Pathogenicity of Treponema denticola Wild-Type and Mutant Strain Tested by an Active Mode of Periodontal Infection Using Microinjection.
Authors: Izard J. , Sasaki H. , Kent R. .
Source: International Journal Of Dentistry, 2012; 2012, p. 549169.
PMID: 22829826
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