6961. Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.
作者: Alexi N Archambault.;Yu-Ru Su.;Jihyoun Jeon.;Minta Thomas.;Yi Lin.;David V Conti.;Aung Ko Win.;Lori C Sakoda.;Iris Lansdorp-Vogelaar.;Elisabeth F P Peterse.;Ann G Zauber.;David Duggan.;Andreana N Holowatyj.;Jeroen R Huyghe.;Hermann Brenner.;Michelle Cotterchio.;Stéphane Bézieau.;Stephanie L Schmit.;Christopher K Edlund.;Melissa C Southey.;Robert J MacInnis.;Peter T Campbell.;Jenny Chang-Claude.;Martha L Slattery.;Andrew T Chan.;Amit D Joshi.;Mingyang Song.;Yin Cao.;Michael O Woods.;Emily White.;Stephanie J Weinstein.;Cornelia M Ulrich.;Michael Hoffmeister.;Stephanie A Bien.;Tabitha A Harrison.;Jochen Hampe.;Christopher I Li.;Clemens Schafmayer.;Kenneth Offit.;Paul D Pharoah.;Victor Moreno.;Annika Lindblom.;Alicja Wolk.;Anna H Wu.;Li Li.;Marc J Gunter.;Andrea Gsur.;Temitope O Keku.;Rachel Pearlman.;D Timothy Bishop.;Sergi Castellví-Bel.;Leticia Moreira.;Pavel Vodicka.;Ellen Kampman.;Graham G Giles.;Demetrius Albanes.;John A Baron.;Sonja I Berndt.;Stefanie Brezina.;Stephan Buch.;Daniel D Buchanan.;Antonia Trichopoulou.;Gianluca Severi.;María-Dolores Chirlaque.;Maria-José Sánchez.;Domenico Palli.;Tilman Kühn.;Neil Murphy.;Amanda J Cross.;Andrea N Burnett-Hartman.;Stephen J Chanock.;Albert de la Chapelle.;Douglas F Easton.;Faye Elliott.;Dallas R English.;Edith J M Feskens.;Liesel M FitzGerald.;Phyllis J Goodman.;John L Hopper.;Thomas J Hudson.;David J Hunter.;Eric J Jacobs.;Corinne E Joshu.;Sébastien Küry.;Sanford D Markowitz.;Roger L Milne.;Elizabeth A Platz.;Gad Rennert.;Hedy S Rennert.;Fredrick R Schumacher.;Robert S Sandler.;Daniela Seminara.;Catherine M Tangen.;Stephen N Thibodeau.;Amanda E Toland.;Franzel J B van Duijnhoven.;Kala Visvanathan.;Ludmila Vodickova.;John D Potter.;Satu Männistö.;Korbinian Weigl.;Jane Figueiredo.;Vicente Martín.;Susanna C Larsson.;Patrick S Parfrey.;Wen-Yi Huang.;Heinz-Josef Lenz.;Jose E Castelao.;Manuela Gago-Dominguez.;Victor Muñoz-Garzón.;Christoph Mancao.;Christopher A Haiman.;Lynne R Wilkens.;Erin Siegel.;Elizabeth Barry.;Ban Younghusband.;Bethany Van Guelpen.;Sophia Harlid.;Anne Zeleniuch-Jacquotte.;Peter S Liang.;Mengmeng Du.;Graham Casey.;Noralane M Lindor.;Loic Le Marchand.;Steven J Gallinger.;Mark A Jenkins.;Polly A Newcomb.;Stephen B Gruber.;Robert E Schoen.;Heather Hampel.;Douglas A Corley.;Li Hsu.;Ulrike Peters.;Richard B Hayes.
来源: Gastroenterology. 2020年158卷5期1274-1286.e12页
Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.
6964. Use of Endoscopic Impression, Artificial Intelligence, and Pathologist Interpretation to Resolve Discrepancies Between Endoscopy and Pathology Analyses of Diminutive Colorectal Polyps.
作者: Neal Shahidi.;Douglas K Rex.;Tonya Kaltenbach.;Amit Rastogi.;Sina Hamidi Ghalehjegh.;Michael F Byrne.
来源: Gastroenterology. 2020年158卷3期783-785.e1页 6966. Oncogenic Mutations in Armadillo Repeats 5 and 6 of β-Catenin Reduce Binding to APC, Increasing Signaling and Transcription of Target Genes.
作者: Pengyu Liu.;Binyong Liang.;Menggang Liu.;Joyce H G Lebbink.;Shan Li.;Manning Qian.;Marla Lavrijsen.;Maikel P Peppelenbosch.;Xin Chen.;Ron Smits.
来源: Gastroenterology. 2020年158卷4期1029-1043.e10页
The β-catenin signaling pathway is one of the most commonly deregulated pathways in cancer cells. Amino acid substitutions within armadillo repeats 5 and 6 (K335, W383, and N387) of β-catenin are found in several tumor types, including liver tumors. We investigated the mechanisms by which these substitutions increase signaling and the effects on liver carcinogenesis in mice.
6967. Interleukin 22 Signaling Regulates Acinar Cell Plasticity to Promote Pancreatic Tumor Development in Mice.
作者: Mirna Perusina Lanfranca.;Yaqing Zhang.;Alexander Girgis.;Samantha Kasselman.;Jenny Lazarus.;Illona Kryczek.;Lawrence Delrosario.;Andrew Rhim.;Lada Koneva.;Maureen Sartor.;Lei Sun.;Christopher Halbrook.;Hari Nathan.;Jiaqi Shi.;Howard C Crawford.;Marina Pasca di Magliano.;Weiping Zou.;Timothy L Frankel.
来源: Gastroenterology. 2020年158卷5期1417-1432.e11页
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that invades surrounding structures and metastasizes rapidly. Although inflammation is associated with tumor formation and progression, little is known about the mechanisms of this connection. We investigate the effects of interleukin (IL) 22 in the development of pancreatic tumors in mice.
6968. Differences in Fecal Microbiomes and Metabolomes of People With vs Without Irritable Bowel Syndrome and Bile Acid Malabsorption.
作者: Ian B Jeffery.;Anubhav Das.;Eileen O'Herlihy.;Simone Coughlan.;Katryna Cisek.;Michael Moore.;Fintan Bradley.;Tom Carty.;Meenakshi Pradhan.;Chinmay Dwibedi.;Fergus Shanahan.;Paul W O'Toole.
来源: Gastroenterology. 2020年158卷4期1016-1028.e8页
Irritable bowel syndrome (IBS) is a heterogeneous disorder, but diagnoses and determination of subtypes are made based on symptoms. We profiled the fecal microbiomes of patients with and without IBS to identify biomarkers of this disorder.
6969. Incidence of Venous Thromboembolism in Patients With Newly Diagnosed Pancreatic Cancer and Factors Associated With Outcomes.
作者: Corinne Frere.;Barbara Bournet.;Sophie Gourgou.;Julien Fraisse.;Cindy Canivet.;Jean M Connors.;Louis Buscail.;Dominique Farge.; .
来源: Gastroenterology. 2020年158卷5期1346-1358.e4页
Pancreatic ductal adenocarcinoma (PDAC) is associated with the highest incidence of venous thromboembolism (VTE) of any cancer type. However, little is known about risk factors for VTE or its outcomes in patients with PDAC.
6972. Lactotrehalose, an Analog of Trehalose, Increases Energy Metabolism Without Promoting Clostridioides difficile Infection in Mice.
作者: Yiming Zhang.;Nurmohammad Shaikh.;Jeremie L Ferey.;Umesh D Wankhade.;Sree V Chintapalli.;Cassandra B Higgins.;Jan R Crowley.;Monique R Heitmeier.;Alicyn I Stothard.;Belgacem Mihi.;Misty Good.;Takanobu Higashiyama.;Benjamin M Swarts.;Paul W Hruz.;Kartik Shankar.;Phillip I Tarr.;Brian J DeBosch.
来源: Gastroenterology. 2020年158卷5期1402-1416.e2页
Trehalose is a disaccharide that might be used in the treatment of cardiometabolic diseases. However, trehalose consumption promotes the expansion of Clostridioides difficile ribotypes that metabolize trehalose via trehalose-6-phosphate hydrolase. Furthermore, brush border and renal trehalases can reduce the efficacy of trehalose by cleaving it into monosaccharides. We investigated whether a trehalase-resistant analogue of trehalose (lactotrehalose) has the same metabolic effects of trehalose without expanding C difficile.
6976. Approaches and Challenges to Management of Pediatric and Adult Patients With Eosinophilic Esophagitis.
Treatment of eosinophilic esophagitis has progressed from elemental formula for children and esophageal dilation for adults to selective exclusion of food triggers and swallowed topical corticosteroids. Management guidelines are available from the American Gastroenterological Association and the Joint Task Force on Allergy Immunology Practice Parameters. We cannot, however, evaluate the efficacy of treatments without a definition of response. We propose a treat-to-target approach, based on symptoms and findings from endoscopy and histology. This approach addresses dissociations between outcomes, such as symptom persistence despite normalization of histologic features and symptom resolution after esophageal dilation despite histologic features of active disease. Eosinophilic esophagitis can now be treated with biologic agents that target specific immune pathways, and findings from prospective trials have indicated that less-restrictive, empiric, elimination diets can be effective and reduce the need for repeated endoscopic assessment of disease activity during food reintroduction. We also discuss eosinophilic esophagitis subtypes, factors associated with disease, and advances in management.
6977. Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium.
作者: Leisha D Nolen.;Stephen M Vindigni.;Julie Parsonnet.; .
来源: Gastroenterology. 2020年158卷5期1197-1201页
Alaska Native (AN) people experience higher incidence of, and mortality from, gastric cancer compared to other U.S. populations, . Compared to the general U.S. population, gastric cancer in AN people occurs at a younger age, is diagnosed at later stages, is more evenly distributed between the sexes, and is more frequently signet-ring or diffuse histology. It is known that the prevalence of Helicobacter pylori (Hp) infection, a risk factor for gastric cancer, is high in AN people; however, high antimicrobial resistance combined with high reinfection rates in Alaska make treatment at the population level complex. In addition, health issues in AN people are uniquely challenging due to the extremely remote locations of many residents. A multiagency workgroup hosted a symposium in Anchorage that brought internationally-recognized experts and local leaders together to evaluate issues around gastric cancer in the AN population. The overall goal of this symposium was to identify the best strategies to combat gastric cancer in the AN population through prevention and early diagnosis.
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