Abstract Previous studies showed that periodontitis and tooth loss are associated with increased risk of pancreatic cancer, suggesting possible role of oral bacteria in the pancreatic cancer etiology. We evaluated whether oral microbiome is associated with risk of pancreatic cancer and pancreatitis. Oral wash samples were collected from 13 pancreatic cancer patients, 3 pancreatitis patients and 12 healthy controls at NYU Langone Medical Center, New York. Ribosomal 16S rRNA genes from oral wash DNA were amplified by universal primers, barcoded, and sequenced with 454 FLX technology. The bacterial 16S rRNA gene sequences were binned into operational taxonomic units (OTUs) with 97% identify and further classified by taxonomy. Non-parametric Wilcoxon Mann Whiteney U test and Kuskal-Wallis test were conducted to compare the relative abundance of taxa across pancreatic cancer, pancreatitis and control groups. A total of 250,008 sequence reads (average 8,928 reads per sample) were observed. Firmicutes, Bacteroidetes, and Actinobacteria are major phyla, accounting for 96.5% of oral microbiota. We found that bacteroides genus was significantly more abundant in both pancreatic cancer patients (p = 0.002) and pancreatitis patients (p = 0.004) compared with control group. Further, BLAST search results indicate that the species most closely represented by the Bacteroides OTUs were oral pathogen. In addition, Corynebacterium (p = 0.033) and Aggregatibacter (p = 0.019) were less abundant in pancreatic cancer and pancretitis groups compared with controls. Data from this pilot study of oral microbiome and pancreatic cancer suggest that the differential abundance in bacteriodates and possibly Corynebacterium and Aggregatibacter, are associated with risk of pancreatic cancer. Bacteroides, Gram-negative bacillus bacteria, plays an important role in oral inflammation, including periodontitis. Further larger studies are warranted to confirm these preliminary findings. Citation Format: I-Hsin Lin, Jing Wu, Steven M. Cohen, Calvin Chen, Darren Bryk, Mollie Marr, Marcovalerio Melis, Elliot Newman, H Leon Pachter, Alexander V. Alekseyenko, Richard B. Hayes, Jiyoung Ahn. Pilot study of oral microbiome and risk of pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 101. doi:10.1158/1538-7445.AM2013-101