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Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study.
Gut. 2018 01; 67(1):120-127.Gut

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.

Authors+Show Affiliations

Department of Population Health, New York University School of Medicine, New York, New York, USA.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.Department of Population Health, New York University School of Medicine, New York, New York, USA.Department of Population Health, New York University School of Medicine, New York, New York, USA.Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.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.Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.Department of Population Health, New York University School of Medicine, New York, New York, USA. NYU Perlmutter Cancer Center, New York, New York, USA.Department of Population Health, New York University School of Medicine, New York, New York, USA. NYU Perlmutter Cancer Center, New York, New York, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27742762

Citation

Fan, Xiaozhou, et al. "Human Oral Microbiome and Prospective Risk for Pancreatic Cancer: a Population-based Nested Case-control Study." Gut, vol. 67, no. 1, 2018, pp. 120-127.
Fan X, Alekseyenko AV, Wu J, et al. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut. 2018;67(1):120-127.
Fan, X., Alekseyenko, A. V., Wu, J., Peters, B. A., Jacobs, E. J., Gapstur, S. M., Purdue, M. P., Abnet, C. C., Stolzenberg-Solomon, R., Miller, G., Ravel, J., Hayes, R. B., & Ahn, J. (2018). Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut, 67(1), 120-127. https://doi.org/10.1136/gutjnl-2016-312580
Fan X, et al. Human Oral Microbiome and Prospective Risk for Pancreatic Cancer: a Population-based Nested Case-control Study. Gut. 2018;67(1):120-127. PubMed PMID: 27742762.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. AU - Fan,Xiaozhou, AU - Alekseyenko,Alexander V, AU - Wu,Jing, AU - Peters,Brandilyn A, AU - Jacobs,Eric J, AU - Gapstur,Susan M, AU - Purdue,Mark P, AU - Abnet,Christian C, AU - Stolzenberg-Solomon,Rachael, AU - Miller,George, AU - Ravel,Jacques, AU - Hayes,Richard B, AU - Ahn,Jiyoung, Y1 - 2016/10/14/ PY - 2016/07/05/received PY - 2016/09/13/revised PY - 2016/09/20/accepted PY - 2016/11/2/pubmed PY - 2017/12/19/medline PY - 2016/10/16/entrez KW - PANCREAS SP - 120 EP - 127 JF - Gut JO - Gut VL - 67 IS - 1 N2 - 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. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/27742762/Human_oral_microbiome_and_prospective_risk_for_pancreatic_cancer:_a_population_based_nested_case_control_study_ L2 - https://gut.bmj.com/lookup/pmidlookup?view=long&pmid=27742762 DB - PRIME DP - Unbound Medicine ER -