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Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study.

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

SUBMITTER: Michaud DS

PROVIDER: S-EPMC3815505 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study.

Michaud Dominique S DS Izard Jacques J Wilhelm-Benartzi Charlotte S CS You Doo-Ho DH Grote Verena A VA Tjønneland Anne A Dahm Christina C CC Overvad Kim K Jenab Mazda M Fedirko Veronika V Boutron-Ruault Marie Christine MC Clavel-Chapelon Françoise F Racine Antoine A Kaaks Rudolf R Boeing Heiner H Foerster Jana J Trichopoulou Antonia A Lagiou Pagona P Trichopoulos Dimitrios D Sacerdote Carlotta C Sieri Sabina S Palli Domenico D Tumino Rosario R Panico Salvatore S Siersema Peter D PD Peeters Petra H M PH Lund Eiliv E Barricarte Aurelio A Huerta José-María JM Molina-Montes Esther E Dorronsoro Miren M Quirós J Ramón JR Duell Eric J EJ Ye Weimin W Sund Malin M Lindkvist Björn B Johansen Dorthe D Khaw Kay-Tee KT Wareham Nick N Travis Ruth C RC Vineis Paolo P Bueno-de-Mesquita H Bas HB Riboli Elio E

Gut 20120918 12

<h4>Objective</h4>Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study.<h4>Design</h4>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.<h4> ...[more]

PMID: 22990306

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Project description:Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. RESULTS:Between July 6, 2005, and April 23, 2007, we enrolled 6363 from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66Â·1% (95% CI 63Â·2â68Â·9) and a specificity of 80Â·6% (79Â·2â82Â·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0Â·018 for RNA sequencing and p=0Â·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0Â·0001 by qRT-PCR) with a sensitivity of 53Â·7% (42Â·6â64Â·3) and a specificity of 82Â·8% (76Â·7â86) in 12 months preceding tuberculosis. Interpretation: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. In this prospective cohort study, we followed up healthy, South African adolescents aged 12â18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex qRT-PCR, the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease.

Dataset Information

Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study.

Publications

Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study.

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