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Original article
Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study
  1. Xiaozhou Fan1,
  2. Alexander V Alekseyenko2,
  3. Jing Wu1,
  4. Brandilyn A Peters1,
  5. Eric J Jacobs3,
  6. Susan M Gapstur3,
  7. Mark P Purdue4,
  8. Christian C Abnet4,
  9. Rachael Stolzenberg-Solomon4,
  10. George Miller5,6,7,
  11. Jacques Ravel8,
  12. Richard B Hayes1,7,
  13. Jiyoung Ahn1,7
  1. 1Department of Population Health, New York University School of Medicine, New York, New York, USA
  2. 2Departments of Public Health Sciences and Oral Health Sciences, Biomedical Informatics Center, Program for Human Microbiome Research, Medical University of South Carolina, Charleston, South Carolina, USA
  3. 3Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA
  4. 4Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  5. 5Department of Surgery, New York University School of Medicine, New York, New York, USA
  6. 6Department of Cell Biology, New York University School of Medicine, New York, New York, USA
  7. 7NYU Perlmutter Cancer Center, New York, New York, USA
  8. 8Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
  1. Correspondence to Dr Jiyoung Ahn, Division of Epidemiology, Department of Population Health, New York University School of Medicine, 650 First Ave, New York, NY 10016, USA; Jiyoung.Ahn{at}nyumc.org

Abstract

Objective A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case–control study.

Design We selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. From pre-diagnostic oral wash samples, we characterised the composition of the oral microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The associations between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, were examined using traditional and L1-penalised least absolute shrinkage and selection operator logistic regression.

Results Carriage of oral pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were associated with higher risk of pancreatic cancer (adjusted OR for presence vs absence=1.60 and 95% CI 1.15 to 2.22; OR=2.20 and 95% CI 1.16 to 4.18, respectively). Phylum Fusobacteria and its genus Leptotrichia were associated with decreased pancreatic cancer risk (OR per per cent increase of relative abundance=0.94 and 95% CI 0.89 to 0.99; OR=0.87 and 95% CI 0.79 to 0.95, respectively). Risks related to these phylotypes remained after exclusion of cases that developed within 2 years of sample collection, reducing the likelihood of reverse causation in this prospective study.

Conclusions This study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer.

  • PANCREAS

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Footnotes

  • Contributors JA had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: XF, RBH and JA. Acquisition of data: JW, EJJ, SMG, MPP, CCA, RS-S and RBH. Analysis and interpretation of data: XF, AVA, JW, BAP, EJJ, SMG, MPP, CCA, RS-S, GM, JR, RBH and JA. Drafting of the manuscript: XF, BAP, RBH and JA. Critical revision of the manuscript for important intellectual content: XF, AVA, JW, BAP, EJJ, SMG, MPP, CCA, RS-S, GM, JR, RBH and JA. Statistical analysis: XF, AVA, RBH and JA. Obtained funding: JA.

  • Funding Research reported in this publication was supported in part by the US National Cancer Institute under award numbers R01CA159036, U01CA182370, R01CA164964, R03CA159414, P30CA016087, R21CA183887 and by AACR/Pancreas Cancer Action Network to J Ahn. The American Cancer Society (ACS) funds the creation, maintenance and updating of the Cancer Prevention Study II cohort.

  • Competing interests None declared.

  • Ethics approval New York University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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