Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
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
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
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- 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
- 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
- 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
- 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, sex, race, date
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, sex, body mass index, race, diabetes mellitus, smoking status, alcohol drinking
Signature 1
Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6
Source: Table 3
Description: Differential microbial abundance between controls and pancreatic cancer cases
Abundance in Group 1: increased abundance in pancreatic cancer cases
| NCBI | Links |
|---|---|
| Alloprevotella | |
| Bacteroidota |
Revision editor(s): Claregrieve1, WikiWorks
Signature 2
Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6
Source: Table 3
Description: Differential microbial abundance between controls and pancreatic cancer cases
Abundance in Group 1: decreased abundance in pancreatic cancer cases
| NCBI | Links |
|---|---|
| Fusobacteriota | |
| Fusobacteriales | |
| Fusobacteriia | |
| Leptotrichia | |
| Leptotrichiaceae |
Revision editor(s): Claregrieve1, WikiWorks
Experiment 2
Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- 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
- 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
- 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 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
- Sequencing type
- 16S
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Roche454
Statistical Analysis
- 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, sex, race, date
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, sex, race, body mass index, smoking status, alcohol drinking, diabetes mellitus
Signature 1
Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6
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 | Links |
|---|---|
| Alloprevotella | |
| Fusobacteriota | |
| Fusobacteriales | |
| Fusobacteriia | |
| Leptotrichia | |
| Leptotrichiaceae |
Revision editor(s): Claregrieve1, WikiWorks
Experiment 3
Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- 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
- 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
- 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 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
- Sequencing type
- 16S
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Roche454
Statistical Analysis
- 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, sex, race, date
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, sex, race, body mass index, smoking status, alcohol drinking, diabetes mellitus
Signature 1
Needs review
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 | Links |
|---|---|
| Leptotrichia | |
| Leptotrichiaceae |
Revision editor(s): Claregrieve1, WikiWorks
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