Xiaozhou Fan1, Alexander V Alekseyenko2, Jing Wu1, Brandilyn A Peters1, Eric J Jacobs3, Susan M Gapstur3, Mark P Purdue4, Christian C Abnet4, Rachael Stolzenberg-Solomon4, George Miller5,6,7, Jacques Ravel8, Richard B Hayes1,7, Jiyoung Ahn1,7. 1. Department of Population Health, New York University School of Medicine, New York, New York, USA. 2. 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. 3. Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA. 4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. 5. Department of Surgery, New York University School of Medicine, New York, New York, USA. 6. Department of Cell Biology, New York University School of Medicine, New York, New York, USA. 7. NYU Perlmutter Cancer Center, New York, New York, USA. 8. Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Authors: Jing Wu; Brandilyn A Peters; Christine Dominianni; Yilong Zhang; Zhiheng Pei; Liying Yang; Yingfei Ma; Mark P Purdue; Eric J Jacobs; Susan M Gapstur; Huilin Li; Alexander V Alekseyenko; Richard B Hayes; Jiyoung Ahn Journal: ISME J Date: 2016-03-25 Impact factor: 10.302
Authors: Eugenia E Calle; Carmen Rodriguez; Eric J Jacobs; M Lyn Almon; Ann Chao; Marjorie L McCullough; Heather S Feigelson; Michael J Thun Journal: Cancer Date: 2002-05-01 Impact factor: 6.860
Authors: Suresh T Chari; Cynthia L Leibson; Kari G Rabe; Lawrence J Timmons; Jeanine Ransom; Mariza de Andrade; Gloria M Petersen Journal: Gastroenterology Date: 2007-10-26 Impact factor: 22.682
Authors: Pedro J Torres; Erin M Fletcher; Sean M Gibbons; Michael Bouvet; Kelly S Doran; Scott T Kelley Journal: PeerJ Date: 2015-11-05 Impact factor: 2.984
Authors: Brandilyn A Peters; Marjorie L McCullough; Mark P Purdue; Neal D Freedman; Caroline Y Um; Susan M Gapstur; Richard B Hayes; Jiyoung Ahn Journal: Cancer Epidemiol Biomarkers Prev Date: 2018-04-27 Impact factor: 4.254
Authors: Joni Leppänen; Olli Helminen; Heikki Huhta; Joonas H Kauppila; Joel Isohookana; Kirsi-Maria Haapasaari; Petri Lehenkari; Juha Saarnio; Tuomo J Karttunen Journal: Virchows Arch Date: 2017-02-12 Impact factor: 4.064
Authors: Richard Meier; Jeffrey A Thompson; Mei Chung; Naisi Zhao; Karl T Kelsey; Dominique S Michaud; Devin C Koestler Journal: Stat Appl Genet Mol Biol Date: 2019-11-08