PT - JOURNAL ARTICLE AU - Xiaozhou Fan AU - Alexander V Alekseyenko AU - Jing Wu AU - Brandilyn A Peters AU - Eric J Jacobs AU - Susan M Gapstur AU - Mark P Purdue AU - Christian C Abnet AU - Rachael Stolzenberg-Solomon AU - George Miller AU - Jacques Ravel AU - Richard B Hayes AU - Jiyoung Ahn TI - Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study AID - 10.1136/gutjnl-2016-312580 DP - 2018 Jan 01 TA - Gut PG - 120--127 VI - 67 IP - 1 4099 - http://gut.bmj.com/content/67/1/120.short 4100 - http://gut.bmj.com/content/67/1/120.full SO - Gut2018 Jan 01; 67 AB - 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.