AGA Abstracts 3 minority groups, with pancreatic cancer nationally has remained unchanged since 2002. Among all 5261 visits of minority patients to our medical center over the past 8 years, 1.3% (66) were in the Emergency Department, 11.1% (585) were in the inpatient setting, and 1.6% (84) were for surgery. These differences are statistically significant for the 3 sites of care (p<0.0001 using chi-square analysis) when compared with White/Non-Hispanic patients (0.2%, 7.3%, and 2.6%, respectively). CONCLUSION: A large percentage of the patients seen at our medical center for pancreatic cancer belong to a minority group but the percentage of these patients is declining, in contrast with the unchanged incidence observed nationally. Minority patients have significantly greater visits to the Emergency Department and inpatient services but significantly fewer surgical visits when compared with White/Non-Hispanic patients. This may reflect advanced stage of disease in the minority population, requiring inpatient care but precluding surgery. The causes of these trends are likely multifactorial but in need of further study in order to understand and improve the management and outcomes of minority patients with pancreas cancer. Sa1960 Mucosal Adherent Bacteria, Inflammation and Colorectal Adenomas Felix Araujo-Perez, Nina Sanapareddy, Amber N. McCoy, Biljana Jovov, Andrew K. Benson, Zaid Abdo, Anthony Fodor, Robert S. Sandler, Temitope O. Keku The gut microbiota is closely involved in normal host physiology and may contribute to the etiology of many diseases. Colorectal cancer (CRC) is the third cause of cancer death in the United States. Evidence from animal and human studies supports a link between inflammation and CRC. However, the contribution of the gut microbiota and local inflamma- tion to sporadic adenomas and CRC in the absence of diagnosed inflammatory bowel disease is not defined. We hypothesized that altered mucosal adherent bacterial composition and increased local inflammation are associated with elevated risk of adenomas. We examined the relationship between adenomas, local mRNA expression of cytokines and adherent bacterial profiles in normal colonic mucosa in a case control study. Methods: Participants were consenting patients undergoing a screening colonoscopy at UNC Hospitals with no history or diagnosis of inflammatory bowel disease. Subjects were defined as cases or controls based on the presence or absence of adenomas. High throughput deep sequencing method was used to assess bacterial diversity in normal colonic mucosa of 80 cases and 87 controls. mRNA gene expression of inflammatory markers in normal colonic tissue were determined by real time RT-PCR. Gene expression relative to the housekeeping gene HMBS was deter- mined by the 2dd CT method. Differences in bacterial profiles between cases and controls were evaluated by t-tests and analysis of similarity matrix. Diversity was measured by Shannon diversity. Logistic regression was used to compute odds ratio (OR) and 95% confidence intervals (CI). Results: Case subjects were more likely to be, male and have higher waist- hip ratio. Compared to the lowest quartile, subjects in the highest tertile of IL-10 gene expression levels were significantly less likely to have adenomas (OR 0.46, 95% CI 0.2- 0.9). The most abundant bacteria in the mucosa were Firmicutes (54%); Bacteroidetes (19%), Proteobacteria (18%), and Cyanobacteria (6%). Compared to controls, cases had lower abundance of Firmicutes (p=0.02) and higher abundance of Cyanobacteria (p=0.04). At the genus level, case subjects showed increased abundance of Acidovorax, Cloacibacterium, Acinetobacter and Lactobacillus and lower abundance of Streptococcus than controls. Increased local IL-17 and IL-23 expression positively correlated with bacterial diversity in cases (r=0.38, p=0.07; r=0.34, p=0.1 respectively) but not controls (r= -0.13, p=0.4; r= -0.03, p=0.8 respectively). IL-10 expression was inversely linked with bacterial diversity in cases (r= -0.39, p=0.05). At the genus level, increased IL-17 and IL-23 expression were associated with elevated abundance of Lactobacillus and Helicobacter. These findings suggest that increased local inflammation is linked with bacterial dysbiosis and may contribute to the etiology of colorectal cancer. Sa1961 Interaction Between Diet and Colonic Microbiota in Low and High Colon Cancer Risk Populations Junhai Ou, Kayellen Umeakunne, James DeLany, H. Rex Gaskins, Keith Newton, Stephen J. O'Keefe The observation that colon cancer is more common in developed than in developing nations suggests that the westernized way of life, and in particular the diet, may be responsible for the increased risk of the disease. Epidemiological surveys, supported by experimental studies, have identified dietary items that can promote and others that appear to suppress colon cancer risk. We have, on the basis of our dietary investigations, suggested that it is the relatively high meat and fat and low complex carbohydrate intakes of the African Americans, who have the highest colon caner risk in US, that places them at higher risk. In contrast, Native Africans whose main dietary staple is corn meal have extremely low risk. METHOD: Stool samples were collected from 12 healthy Africans (NA) and 12 healthy African Americans (AA) matched for age, sex and BMI. DNA from fecal samples was isolated and purified by the QIAamp DNA Stool Mini Kit (Qiagen, Valencia, CA) in combination with the FastPrep- 24 System (MP Biomedicals, Solon, OH). qPCR were performed using an Applied Biosystems 7900HT Fast Real-Time PCR System. 16S rRNA genes were used to target total and specific bacteria known to influence mucosal health, but methyl coenzyme-M reductase A gene (mcrA) for methanogen and dissimilatory sulfite reductase gene (dsrA) for Sulfate reducing bacteria. Stool short chain fatty acids (SCFAs) were measured by gas chromatography. RESULTS: Major SCFAs were significant higher in stools from NA.. Total bacteria, select butyrate producing bacteria (Faecalibacterium prausnitzii and Clostridium IV) and methanog- ens were higher in the stool samples from NA as well (Table 1 and Table 2). CONCLUSION: These results suggest that the low colon cancer risk in native Africans may be a consequence of their high dietary intakes of complex carbohydrate and low meat consumption, stimulating fermentation, butyrogenesis, and methanogenesis, in conjuction with the induction of mucosal anti-inflammatory properties of F prausnitzii and Clostriium IV. Table 1. Major SCFA level in stool (umole/per g feces) S-356 AGA Abstracts Table 2: Stool bacteria levels (copies/per mg feces) Sa1962 Acetylcarnitine Potentiates the Anticarcinogenic Effects of Butyrate on Colon Cancer Cells Ernest G. Seidman, Serge Dionne, Ihsan El Imrani, Dan Saragosti, Emile Levy AIMS: Butyrate, a short-chain fatty acid , is a potent anticarcinogenic compound for colon cancer cells. However, its rapid metabolism by colonic epithelial cells is hypothesized to limit its anticancer benefits. Carnitine is essential to fatty acid oxidation and carnitine depletion is implicated in the inability of mitochondria to maintain normal metabolism. The aims of this study were to evaluate the effect of carnitine and acetylcarnitine (ALCAR) on the response of colon carcinoma cells to butyrate and to explore the underlying mechanisms. METHODS: SW480 cells were incubated with butyrate +/- carnitine or ALCAR. Cell viability was assessed with MTT and trypan blue exclusion. Apoptosis was measured with the M30 assay. Carnitine uptake was assessed using [3H]-carnitine. Modulation of proteins implicated in carnitine transport, as well as in cell death and proliferation was assessed by Western blot. RESULTS: SW480 cells expressed higher levels of OCTN2 and displayed 8 fold higher carnitine uptake than undifferentiated Caco-2 cells (0.33 vs. 0.042 pmol/min/mg protein, p<0.01). Butyrate induced SW480 cell death at concentrations of 2mM and higher. ALCAR (5 mM) alone, but not carnitine, significantly increased cell death rate (10.2 vs. 4.6 %, p<0.01). Cells treated with 3 mM butyrate combined with ALCAR displayed increased mortality (29 vs. 21%, p<0.05). The effects of ALCAR could not be reproduced by acetate or acetate + carnitine. Butyrate induced apoptosis in SW480 cells, while carnitine and its acetylated congener had no independent effect. The addition of carnitine or ALCAR increased butyrate-induced apoptosis by 8-13% (p=NS). Butyrate increased levels of cyclin D1 and p21 (125 and 270 % of control levels, p<0.01). PARP cleavage, a marker of caspase activity, was increased 6 fold, while Bcl-XL and survivin levels were decreased by butyrate (61 and 46%, respectively, p<0.01). Butyrate also downregulated dephospho-β-catenin and increased acetylated histone H4 levels (2.6 fold, p<0.01). The effect of carnitine and ALCAR on these proteins was also determined. At butyrate concentrations of 2 mM and below, carnitine consistently decreased survivin levels by at least 25% (p<0.05). ALCAR independently induced a 20% decrease in p21 (p<0.05). Acetylation of histone H4 as well as dephospho- β-catenin levels were not affected by ALCAR and carnitine. CONCLUSIONS: These results demonstrate that butyrate and ALCAR are potentially beneficial anticarcinogenic nutrients that inhibit colon cancer cell survival. The combination of both agents may have superior anticarcinogenic properties than butyrate alone. Supported by a grant from the Dairy Founda- tion of Canada and NSERC. Sa1963 Increased Levels of Serum Glucose-Dependent Insulinotropic Polypeptide as a Novel Risk Factor for Human Colorectal Adenoma Yu Sasaki, Hiroaki Takeda, Takeshi Sato, Tomohiko Orii, Shoichi Nishise, Ko Nagino, Daisuke Iwano, Takao Yaoita, Kazuya Yoshizawa, Sumio Kawata Objectives: Obesity and insulin resistance are thought to be risk factors for colorectal adenoma. Glucose-dependent insulinotropic polypeptide (GIP) stimulates insulin secretion from the pancreas and promotes fat accumulation in adipocytes. The association between serum GIP and the risk of colorectal adenoma has not been examined previously. Methods: We investigated this association in 370 subjects who underwent total colonoscopy during thorough physical check-ups between January and December, 2008. We employed a cross- sectional design, and classified the subjects into a colorectal adenoma group and a control group without adenoma, according to their endoscopic findings. Serum GIP concentrations in samples of venous blood obtained after an overnight fast were measured using a sandwich ELISA kit. Results: The mean levels of fasting GIP (34.9 ± 49.5 pg/ml vs. 25.0 ± 20.1 pg/ ml; p = 0.047), triglyceride, glucose, insulin and values of homeostasis model assessment- insulin resistance in the colorectal adenoma group were significantly higher than those in the control group. When restricted to male subjects, the adenoma group (36.6 ± 52.7 pg/ ml) had a significantly higher fasting GIP concentration than the control group (23.7 ± 15.6 pg/ml; p = 0.027). In contrast, in female subjects, no significant difference in GIP concentra- tion was observed between the groups. Multiple logistic regression analysis showed that the top quartile of fasting GIP levels was associated with a significantly high risk of colorectal adenoma (odds ratio 2.1, 95% confidence interval 1.08-3.96, p = 0.01) in comparison with the bottom quartile. Quartile analysis demonstrated that increased levels of GIP were related to increased levels of fasting insulin and values of homeostasis model assessment (HOMA) β-cell. Conclusions: These results suggest that an increased level of fasting GIP as well as high levels of fasting insulin and glucose are associated with an increased risk of colorectal adenoma, and may offer a new insight into the role of GIP in the development of human colorectal adenoma.