Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Fan X, Alekseyenko AV, Wu J, Peters BA, Jacobs EJ, Gapstur SM, Purdue MP, Abnet CC, Stolzenberg-Solomon R, Miller G, Ravel J, Hayes RB, Ahn J
Journal
Gut
Year
2018
Keywords:
PANCREAS
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.

Experiment 1


Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Pancreatic carcinoma cancer of pancreas,cancer of the pancreas,carcinoma of exocrine pancreas,carcinoma of pancreas,carcinoma of the pancreas,exocrine cancer,exocrine pancreas carcinoma,exocrine pancreatic carcinoma,pancreas cancer,pancreas carcinoma,pancreatic cancer,pancreatic cancer (not islets),pancreatic carcinoma,pancreatic carcinoma, familial,Pancreatic carcinoma
Group 0 name Corresponds to the control (unexposed) group for case-control studies
controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
pancreatic cancer cases
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
subjects from the two cohorts with incident primary pancreatic adenocarcinoma
Group 0 sample size Number of subjects in the control (unexposed) group
371
Group 1 sample size Number of subjects in the case (exposed) group
361

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Logistic Regression
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
Matched on Factors on which subjects have been matched on in a case-control study
age, date, race, sex, Matched on: "cohort" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.cohort
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, alcohol drinking, body mass index, diabetes mellitus, race, sex, smoking status


Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): Claregrieve1, WikiWorks

Source: Table 3

Description: Differential microbial abundance between controls and pancreatic cancer cases

Abundance in Group 1: increased abundance in pancreatic cancer cases

NCBI Quality ControlLinks
Alloprevotella
Bacteroidota

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): Claregrieve1, WikiWorks

Source: Table 3

Description: Differential microbial abundance between controls and pancreatic cancer cases

Abundance in Group 1: decreased abundance in pancreatic cancer cases

NCBI Quality ControlLinks
Fusobacteriota
Fusobacteriales
Fusobacteriia
Leptotrichia
Leptotrichiaceae

Revision editor(s): Claregrieve1, WikiWorks

Experiment 2


Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
subjects from the CPSII cohorts with incident primary pancreatic adenocarcinoma
Group 0 sample size Number of subjects in the control (unexposed) group
170
Group 1 sample size Number of subjects in the case (exposed) group
170

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): Claregrieve1, WikiWorks

Source: Supplementary Table 3a

Description: Median relative abundance of selected oral microbiota in pancreatic cancer cases and controls in the Cancer Prevention Study(CPS) cohort

Abundance in Group 1: decreased abundance in pancreatic cancer cases

NCBI Quality ControlLinks
Alloprevotella
Fusobacteriota
Fusobacteriales
Fusobacteriia
Leptotrichia
Leptotrichiaceae

Revision editor(s): Claregrieve1, WikiWorks

Experiment 3


Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
subjects from the PLCO cohorts with incident primary pancreatic adenocarcinoma
Group 0 sample size Number of subjects in the control (unexposed) group
201
Group 1 sample size Number of subjects in the case (exposed) group
191

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): Claregrieve1, WikiWorks

Source: Supplementary Table 3b

Description: Median relative abundance of selected oral microbiota in pancreatic cancer cases and controls in the Cancer Prevention Study(CPS) cohort

Abundance in Group 1: decreased abundance in pancreatic cancer cases

NCBI Quality ControlLinks
Leptotrichia
Leptotrichiaceae

Revision editor(s): Claregrieve1, WikiWorks