title: Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study.
abstract: 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.
  
  
  
  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.
  
  
  
  Carriage of oral pathogens,Porphyromonas gingivalisandAggregatibacter 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). PhylumFusobacteriaand its genusLeptotrichiawere 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.
  
  
  
  This study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer.
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, New York, USA.
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Fan
authors.affiliation: Departments 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.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Alekseyenko
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, New York, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, New York, USA.
authors.forename: Brandilyn A
authors.identifier: 0000-0002-1534-2578
authors.initials: BA
authors.lastname: Peters
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jacobs
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Purdue
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Stolzenberg-Solomon
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, USA.|Department of Cell Biology, New York University School of Medicine, New York, New York, USA.|NYU Perlmutter Cancer Center, New York, New York, USA.
authors.forename: George
authors.initials: G
authors.lastname: Miller
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Ravel
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, New York, USA.|NYU Perlmutter Cancer Center, New York, New York, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, New York, USA.|NYU Perlmutter Cancer Center, New York, New York, USA.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Ahn
mesh_terms: D000230:Adenocarcinoma / Q000382:microbiology*; D000368:Aged; D016976:Aggregatibacter actinomycetemcomitans / Q000302:isolation & purification; D002353:Carrier State / Q000382:microbiology; D016022:Case-Control Studies; D005260:Female; D045182:Fusobacteria / Q000302:isolation & purification; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D009055:Mouth / Q000382:microbiology*; D010190:Pancreatic Neoplasms / Q000382:microbiology*; D010519:Periodontium / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000302:isolation & purification; D011446:Prospective Studies; D012307:Risk Factors
keywords: PANCREAS