AGA Abstracts Mo1780 GENDER BIAS IN REFERRAL AND DIAGNOSIS OF INFLAMMATORY BOWEL DISEASE IN A CANADIAN INCEPTION COHORT John I. Oshiomogho, Joelle St-Pierre, Blessing Odia, Gilaad Kaplan, Remo Panaccione, Cynthia H. Seow, Gurmeet K. Bindra, Jose G. Ferraz, Yasmin Nasser, Paul L. Beck, Humberto Jijon Background: Delay in diagnosis of inflammatory bowel disease (IBD) can lead to adverse outcomes. The greater Calgary area, a city of 1.5 million, is served by a central triage system which receives >1600 referrals per month. Wait times to see a gastroenterologist in Canada can exceed 18 months for symptoms such as abdominal pain or non-bloody diarrhea, common presenting symptoms of IBD. To expedite the diagnosis of IBD a “High-Risk IBD clinic” (HR-IBD) was established. Recent studies report that gender, age, and environment impact the incidence of IBD with females having a higher risk of Crohn's disease (CD) over the age of 14y whereas males a higher incidence of ulcerative colitis (UC) over the age of 45y. These differences in IBD incidence also appear to be influenced by environment and geography. Aim: To examine referral and decision practices within an urgent IBD clinical care pathway for early diagnosis and treatment of patients with IBD. Methods: We performed a retrospective chart review of patients referred to the HR-IBD clinic at the University of Calgary (2014 to 2017). Patients referred to this clinic did not have a pre-existing diagnosis of IBD but were felt to be at increased risk based on the review of the referral by a staff gastroenterologist. Results: 257 patients were triaged to the HR-IBD clinic of which 211 agreed to participate in the study. The average age was 36.2y for female and 35.9y for males; 68.2% were female and 31.8% males. Males had a higher incidence of bleeding (62.7% vs 46.7%), weight loss (33.3% vs 15.6%) and a family history of IBD (35.6% vs 28.2) or rheumatological disease (32.3% vs 25.0%). Women had a high incidence of abdominal pain (58.7% vs 48.4%), perianal pain (5.6% vs 0%) and a similar incidence of diarrhea (71.6% vs 68.2%). Males were more likely to have anemia (14.9% vs 9.8%), abnormal ferritin (21.6% vs 11.8%) but near identical incidence of elevated CRP (50.7% vs 49.3). 60 pts were diagnosed with IBD (28.6% of all pts). Interestingly, although women were ~2- fold more likely to be triaged to the HR-IBD clinic, they were less likely to be diagnosed with IBD (22.2% of females vs. 42.4% males). CD was diagnosed in 13.2% of females and 28.3% of males and UC was diagnosed in 9.0% of females and 13.4% of males. Females were five times more likely to be diagnosed with irritable bowel syndrome than males (26.2% versus 4.3%). Discussion and Conclusions: Based on a review of consult requests, we found that women were more commonly referred for urgent IBD investigation than males even when males had similar rates of recognized “red flags” including; bleeding, anemia, positive family history of IBD and rheumatological disease. Ultimately, of those referred for urgent assess- ment, 42% of males were diagnosed with IBD versus 22.2% of females suggesting a strong gender bias in referral for investigation of new onset IBD. Mo1781 ROLE OF G PROTEIN-COUPLED RECEPTOR 15 IN COLON CANCER. Hong Namkoong, Bomi Lee, Seong-Joon Koh, Stephan Rogalla, Aida Habtezion Background: Leukocytes recruitment maintains intestinal immune homeostasis and responses. Several studies find a positive correlation between increased infiltration and high densities of CD3+ T cells (CD4 and CD8 T eff cells) at tumor sites and disease-free survival in colorectal cancer (CRC). G protein-coupled receptor 15 (GPR15) is structurally related to known lymphocyte trafficking receptors, and recent studies highlighted a role for GPR15 as a T cell homing molecule in both mouse and human colon, however the role of GPR15 in CRC remains to be defined. Methods: In human CRC study, immune cells were isolated from tumor tissues and healthy surgical tumor margins (STM), and their proportions as well as expression of GPR15 was analyzed by flow cytometry. In mouse studies, colon cancer was induced in GPR15-deficient (KO) and GPR15-suficient (Het) mice using azoxymethane (AOM) and dextran sulfate sodium (DSS). A single dose of AOM (10 mg/kg) was administered intraperitoneally followed by repeated cycles of 2% DSS solution in drinking water. Serial endoscopy was performed in mice to monitor and visualize the distal region of colon. Mice were euthanized 10 weeks after the initial DSS administration, and the colon length and the number of polyps were recorded. Immune cells were isolated from the mice colons and assessed by flow cytometry. Results: Our studies in human CRC showed differential GPR15 expression in the tumor versus “healthy” surgical tumor margins (STM). GPR15+ immune cells were significantly reduced in the human colon tumors compared to STMs. In the AOM- DSS mouse model, we found that the number of colonic polyps were significantly increased in GPR15 KO compared to GPR15-Het mice. Moreover, GPR15-KO mice showed severe body weight loss, shorter colon length, and increased number of colonic polyps than GPR15- Het mice suggesting GPR15-KO mice were more susceptible to develop CRC. Analysis of immune cell infiltrates in the colonic polyps showed significantly decreased T cells, specifically CD8+ T cells in GPR15-KO mice as compared to GPR15-Het mice. GPR15 deficiency likely S-836 AGA Abstracts alters the immune environment in colonic polyps mitigating T-cell mediated anti-tumor response. Conclusions Our findings suggest an immunomodulatory role for GPR15 in CRC. Taken together, we propose that GPR15 represents a novel, colon-specific therapeutic target for CRC. Mo1782 THE ROLE OF CYCLOOXYGENASE IN COLITIS-ASSOCIATED COLORECTAL CANCER Hayley Good, Alice E. Shin, Liyue Zhang, David Meriwether, Srinivasa Reddy, Timothy C. Wang, Elena N. Fazio, Samuel Asfaha Introduction: Colorectal cancer (CRC) is the 2 nd leading cause of cancer death in North America. Inflammatory bowel disease (IBD), a chronic state of colonic inflammation, is a major risk factor for CRC. Despite the clear link between inflammation and cancer, the mechanism by which colitis leads to cancer is unknown. We previously showed that Dclk1- expressing tuft cells are quiescent, long-lived, and remain resistant to proliferation even upon mutation of the tumor suppressor APC. Following colitis, however, APC-mutated cells become cancer-initiating cells by a mechanism not fully understood. Interestingly, Dclk1+ tuft cells express high levels of cyclooxygenase (COX)-1 and -2, the direct enzyme target of non-steroidal anti-inflammatory drugs (NSAIDs) which are also known to be chemopreven- tative for CRC. Aim: In the present study, we aim to examine the effects of cyclooxygenase inhibition on colitis-associated cancer (CAC). Methods: Dclk1 CreERT2 /APC fl/fl mice were administered tamoxifen to induce an APC mutation in Dclk1-expressing cells. Mice were then exposed to the colitis-inducing agent dextran sodium sulfate (DSS), followed by daily treatment with Aspirin (non-selective COX inhibitor), celecoxib or rofecoxib (COX-2 inhibi- tors), SC-560 (COX-1 inhibitor), or vehicle, for the experiment duration. Additionally, we followed the same experimental protocol to test the effects of NSAIDs in the AOM/DSS model of CAC. The carcinogen azoxymethane (AOM), followed by DSS, were administered to induce tumorigenesis. Sixteen weeks post-tamoxifen or AOM, colonic tumor number and size were examined to determine the effect of NSAIDs on tumor initiation and growth, respectively. The extent of inflammation was assessed by myeloperoxidase (MPO) activity and histology. Finally, colonic eicosanoid levels were measured by liquid chromatography- mass spectrometry (LC-MS) and mRNA levels of inflammatory mediators were assessed by qRT-PCR. Results: LC-MS analysis of eicosanoids in colonic tissue during colitis revealed that Aspirin and SC-560, but not celecoxib, significantly reduced COX-derived prostaglandin levels. Treatment of mice with Aspirin, but not COX-2 inhibitors, significantly reduced the number of colonic tumors in both Dclk1+ cell-derived and AOM/DSS models of CAC. The COX-1 inhibitor, SC-560, also significantly reduced colonic tumor number. We detected no difference in tumor size or severity of colitis between vehicle and NSAID-treated groups. Interestingly, Aspirin was associated with a significant reduction in Dclk1+ cell number, suggesting an important role for prostaglandins in Dclk1+ cell survival. Conclusion: These findings suggest a role for cyclooxygenase in CAC. Our results suggest that Aspirin is chemopreventative in CAC, potentially through inhibition of the production of COX-1- mediated prostaglandins that may be critical for Dclk1+ cell survival. Mo1783 H. PYLORI-INDUCED PRDX2 PROTECTS AGAINST OXIDATIVE STRESS AND PROMOTES RESISTANCE TO CISPLATIN Sen Wang, Zheng Chen, Heng Lu, Shoumin Zhu, Dunfa Peng, Mohammed Soutto, Ahmed R. Gomaa, Nadeem Bhat, Huma Naz, Hao Xu, Zekuan Xu, Wael El-Rifai Background & Aims: The antioxidant enzyme peroxiredoxin 2 (PRDX2) plays a critical role in regulating reactive oxygen species (ROS) levels in several diseases. Helicobacter pylori (H. pylori) infection is a well-known risk factor of gastric cancer. The role of PRDX2 in gastric tumorigenesis remains largely unknown. We investigated the molecular function and regulation of PRDX2 in response to infection with H. pyloriand cisplatin treatment in gastric cancer cells. Methods: Western blots (WB) and quantitative real-time PCR (qPCR) analysis were performed on AGS, SNU-1 and MKN28 gastric cancer cell lines to detect PRDX2 expression levels with or without H. pyloriinfection (7.13 or J166 strain). We evaluated the levels of ROS by H2DCFDA staining. Western blot (WB) analysis was used to determine oxidative DNA damage and double stranded DNA breaks by using antibodies against 8- Oxo-guanine and p-H 2 AX. WB and NF-kb luciferase reporter assay were performed to investigate the link between PRDX2 and NF-kb signaling. ATP-GLO cell titer analysis was utilized to determine cell viability. Results: Our data indicated that PRDX2 mRNA and protein expression levels were induced by H. pylori in AGS and SNU-1 cells. WB analysis on gastric tissues collected from mice infected with H. pylori, for 1 and 2 weeks, demonstrated an increase in expression of PRDX2. The PRDX2 knockdown significantly increased ROS levels and 8-Oxoguanine staining for WB data showing that p-H 2 A.X protein level was strongly induced in PRDX2 knockdown and H. pylori infected cells. Interestingly, WB data showed that TNF-αtreatment induced PRDX2 protein levels while Bay 11-7082 treatment, inhibitor of NF-kB, decreased PRDX2 protein level in AGS and SNU-1 cells. At the same time, PRDX2 transient knockdown in both AGS and SNU-1 cells decreased p-P65 (S536) protein expression levels and luciferase reporter activity (P<0.05), suggesting the presence of a feed forward loop between NF-kB and PRDX2. Interestingly, we found that cells resistant to cisplatin express higher levels of PRDX2, as compared to their parental cells. inhibition of PRDX2 significantly sensitized AGS and SNU-1 cells to cisplatin treatment. Conclusion: Our in vitro and in vivo data indicate that PRDX2 is induced in response to H. pylori infection. Our results suggest a positive feedforward loop between PRDX2 and NF-kB. PRDX2 protects against ROS and DNA damage to promote cell survival in response to H. pylori and cisplatin treatment.