Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer
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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
Authors
Hayes RB, Ahn J, Fan X, Peters BA, Ma Y, Yang L, Agalliu I, Burk RD, Ganly I, Purdue MP, Freedman ND, Gapstur SM, Pei Z
Journal
JAMA oncology
Year
2018
Importance: Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC. Objective: To prospectively examine associations between the oral microbiome and incident HNSCC. Design, Setting, and Participants: This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline. Exposures: Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P-value (q-value) <.10 were considered significant. Main Outcomes and Measures: Incident HNSCC. Results: The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco smokers, tended to have greater alcohol consumption (among drinkers), and to be positive for oral carriage of papillomavirus-16. Overall microbiome composition was not associated with risk of HNSCC. Greater abundance of genera Corynebacterium (fold change [FC], 0.58; 95% confidence interval [CI], 0.41-0.80; q = .06) and Kingella (FC, 0.63; 95% CI, 0.46-0.86; q = .08) were associated with decreased risk of HNSCC, potentially owing to carcinogen metabolism capacity. These findings were consistent for both cohorts and by cohort follow-up time. The observed relationships tended to be stronger for larynx cancer and for individuals with a history of tobacco use. Conclusions and Relevance: This study demonstrates that greater oral abundance of commensal Corynebacterium and Kingella is associated with decreased risk of HNSCC, with potential implications for cancer prevention.
Experiment 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
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
- Head and neck squamous cell carcinoma carcinoma of the head and neck,craniocervical region squamous cell carcinoma,head and neck squamous cell carcinoma,HNSCC,SCCHN,squamous cell carcinoma of head and neck,squamous cell carcinoma of the head and neck,squamous cell carcinoma, head and neck,squamous cell carcinomas of head and neck,Head and neck squamous cell 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
- HNSCC
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- histologically confirmed incident HNSCC including oral cavity, pharynx and larynx. (excluding salivary glands & nasopharynx)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 254
- Group 1 sample size Number of subjects in the case (exposed) group
- 129
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
- DESeq2
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.1
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
- Matched on Factors on which subjects have been matched on in a case-control study
- age, ethnic group, sex, date
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, sex, alcohol drinking, smoking behavior
Alpha Diversity
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Table 2
Description: Differential microbial abundance between controls and HNSCC patients
Abundance in Group 1: increased abundance in HNSCC
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota |
Revision editor(s): Claregrieve1, WikiWorks
Signature 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Table 2
Description: Differential microbial abundance between controls and HNSCC patients
Abundance in Group 1: decreased abundance in HNSCC
| NCBI | Quality Control | Links |
|---|---|---|
| Betaproteobacteria | ||
| Capnocytophaga leadbetteri | ||
| Corynebacterium | ||
| Kingella | ||
| Hoylesella nanceiensis | ||
| Selenomonas sputigena |
Revision editor(s): Claregrieve1, WikiWorks
Experiment 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Squamous cell carcinoma carcinoma, squamous cell, malignant,epidermoid carcinoma,epidermoid cell cancer,malignant epidermoid cell neoplasm,malignant epidermoid cell tumor,malignant squamous cell neoplasm,malignant squamous cell tumor,squamous carcinoma,squamous cell cancer,squamous cell carcinoma,squamous cell carcinoma (morphologic abnormality),squamous cell carcinoma NOS (morphologic abnormality),squamous cell epithelioma,Squamous cell carcinoma
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Larynx cancer cases
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- histologically confirmed incident HNSCC involving the larynx
- Group 1 sample size Number of subjects in the case (exposed) group
- 58
Lab analysis
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- ethnic group, sex, age, date
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, sex, smoking status, alcohol drinking
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Table 2, Supplementary Table 6, Text
Description: Differential microbial abundance between controls and larynx cancer patients
Abundance in Group 1: decreased abundance in Larynx cancer cases
| NCBI | Quality Control | Links |
|---|---|---|
| Abiotrophia | ||
| Betaproteobacteria | ||
| Capnocytophaga | ||
| Corynebacterium | ||
| Kingella | ||
| Kingella denitrificans | ||
| Neisseria | ||
| Neisseriales | ||
| Streptococcus sanguinis |
Revision editor(s): Claregrieve1, WikiWorks
Experiment 3
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Pharynx cancer cases
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- histologically confirmed incident HNSCC involving the pharynx
- Group 1 sample size Number of subjects in the case (exposed) group
- 30
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Table 2, Supplementary Table 6, Text
Description: Differential microbial abundance between controls and pharynx cancer patients
Abundance in Group 1: decreased abundance in Pharynx cancer cases
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomyces oris | ||
| Betaproteobacteria | ||
| Corynebacterium | ||
| Kingella | ||
| Neisseriales | ||
| Veillonella denticariosi |
Revision editor(s): Claregrieve1, WikiWorks
Experiment 4
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Oral cavity cancer cases
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- histologically confirmed incident HNSCC involving the oral cavity
- Group 1 sample size Number of subjects in the case (exposed) group
- 41
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Table 2, Supplementary Table 6, Text
Description: Differential microbial abundance between controls and oral cavity cancer patients
Abundance in Group 1: increased abundance in Oral cavity cancer cases
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomyces |
Revision editor(s): Claregrieve1, WikiWorks
Signature 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Table 2, Supplementary Table 6, Text
Description: Differential microbial abundance between controls and oral cavity cancer patients
Abundance in Group 1: decreased abundance in Oral cavity cancer cases
| NCBI | Quality Control | Links |
|---|---|---|
| Neisseria sicca | ||
| Parvimonas micra |
Revision editor(s): Claregrieve1, WikiWorks
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