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Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk.

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dc.contributor.authorYuan, Fangcheng
dc.contributor.authorHung, Rayjean J
dc.contributor.authorWalsh, Naomi
dc.contributor.authorZhang, Han
dc.contributor.authorPlatz, Elizabeth A
dc.contributor.authorWheeler, William
dc.contributor.authorSong, Lei
dc.contributor.authorArslan, Alan A
dc.contributor.authorBeane Freeman, Laura E
dc.contributor.authorBracci, Paige
dc.contributor.authorCanzian, Federico
dc.contributor.authorDu, Mengmeng
dc.contributor.authorGallinger, Steven
dc.contributor.authorGiles, Graham G
dc.contributor.authorGoodman, Phyllis J
dc.contributor.authorKooperberg, Charles
dc.contributor.authorLe Marchand, Loic
dc.contributor.authorNeale, Rachel E
dc.contributor.authorRosendahl, Jonas
dc.contributor.authorScelo, Ghislaine
dc.contributor.authorShu, Xiao-Ou
dc.contributor.authorVisvanathan, Kala
dc.contributor.authorWhite, Emily
dc.contributor.authorZheng, Wei
dc.contributor.authorAlbanes, Demetrius
dc.contributor.authorAmiano, Pilar
dc.contributor.authorAndreotti, Gabriella
dc.contributor.authorBabic, Ana
dc.contributor.authorBamlet, William R
dc.contributor.authorBerndt, Sonja I
dc.contributor.authorBrennan, Paul
dc.contributor.authorBueno-de-Mesquita, Bas
dc.contributor.authorBuring, Julie E
dc.contributor.authorCampbell, Peter T
dc.contributor.authorChanock, Stephen J
dc.contributor.authorFuchs, Charles S
dc.contributor.authorGaziano, J Michael
dc.contributor.authorGoggins, Michael G
dc.contributor.authorHackert, Thilo
dc.contributor.authorHartge, Patricia
dc.contributor.authorHassan, Manal M
dc.contributor.authorHolly, Elizabeth A
dc.contributor.authorHoover, Robert N
dc.contributor.authorKatzke, Verena
dc.contributor.authorKirsten, Holger
dc.contributor.authorKurtz, Robert C
dc.contributor.authorLee, I-Min
dc.contributor.authorMalats, Nuria
dc.contributor.authorMilne, Roger L
dc.contributor.authorMurphy, Neil
dc.contributor.authorNg, Kimmie
dc.contributor.authorOberg, Ann L
dc.contributor.authorPorta, Miquel
dc.contributor.authorRabe, Kari G
dc.contributor.authorReal Arribas, Francisco
dc.contributor.authorRothman, Nathaniel
dc.contributor.authorSesso, Howard D
dc.contributor.authorSilverman, Debra T
dc.contributor.authorThompson, Ian M
dc.contributor.authorWactawski-Wende, Jean
dc.contributor.authorWang, Xiaoliang
dc.contributor.authorWentzensen, Nicolas
dc.contributor.authorWilkens, Lynne R
dc.contributor.authorYu, Herbert
dc.contributor.authorZeleniuch-Jacquotte, Anne
dc.contributor.authorShi, Jianxin
dc.contributor.authorDuell, Eric J
dc.contributor.authorAmundadottir, Laufey T
dc.contributor.authorLi, Donghui
dc.contributor.authorPetersen, Gloria M
dc.contributor.authorWolpin, Brian M
dc.contributor.authorRisch, Harvey A
dc.contributor.authorYu, Kai
dc.contributor.authorKlein, Alison P
dc.contributor.authorStolzenberg-Solomon, Rachael
dc.contributor.funderNIH - National Cancer Institute (NCI) (Estados Unidos)
dc.date.accessioned2024-02-13T11:27:33Z
dc.date.available2024-02-13T11:27:33Z
dc.date.issued2020-09-15
dc.description.abstractRegistry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipThis research is supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, NCI, NIH. We thank Laurie Burdett, Aurelie Vogt, Belynda Hicks, Amy Hutchinson, Meredith Yeager, and other staff at the NCI's Division of Epidemiology and Genetics (DECG) Cancer Genomics Research Laboratory (CGR) for GWAS genotyping. The IARC/Central Europe study was supported by a grant from the NCI at the NIH (R03 CA123546-02) and grants from theMinistry of Health of the Czech Republic (NR 9029-4/2006, NR9422-3, NR9998-3, MH CZDRO-MMCI 00209805). The work at Johns Hopkins University was supported by the NCI grants P50CA062924, R01CA97075, and P30 CA006973. Additional support was provided by the Lustgarten Foundation, Susan Wojcicki and Dennis Troper, and the Sol Goldman Pancreas Cancer Research Center. This work was supported by RO1 CA154823 and federal funds from the NCI, NIH under contract number HHSN261200800001E. The Mayo Clinic Biospecimen Resource for Pancreas Research study is supported by the Mayo Clinic SPORE in Pancreatic Cancer (P50 CA102701). The Memorial Sloan Kettering Cancer Center Pancreatic Tumor Registry is supported by P30CA008748, the Geoffrey Beene Foundation, the Arnold and Arlene Goldstein Family Foundation, and the Society of MSKCC. We acknowledge the contribution of Dr. Irene Orlow to the study. The Queensland Pancreatic Cancer Study was supported by a grant from the National Health and Medical Research Council of Australia (NHMRC; grant number: 442302). R.E. Neale is supported by aNHMRCSenior Research Fellowship (#1060183). The UCSF pancreas study was supported by NIH-NCI grants (R01CA1009767, R01CA109767-S1, and R01CA059706) and the Joan Rombauer Pancreatic Cancer Fund. Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program; the NCI's SEER Program under contract HSN261201000140C awarded to CPIC; and the CDC's National Program of Cancer Registries, under agreement #U58DP003862-01 awarded to the California Department of Public Health. The Yale (CT) pancreas cancer study was supported by NCI at the NIH (grant number 5R01CA098870). The cooperation of 30 Connecticut hospitals, including Stamford Hospital, in allowing patient access, is gratefully acknowledged. The Connecticut Pancreas Cancer Study was approved by the State of Connecticut Department of Public Health Human Investigation Committee. Certain data used in that study were obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health. The authors assume full responsibility for analyses and interpretation of these data. Studies included in PANDoRA were partly funded by: the Czech Science Foundation (no. P301/12/1734), the Internal Grant Agency of the Czech Ministry of Health (IGA NT 13 263); the BadenWuurttemberg State Ministry of Research, Science and Arts (Prof. H. Brenner), the Heidelberger EPZ-Pancobank (Prof. M.W. Buuchler and team: Prof. T. Hackert, Dr. N.A. Giese, Dr. Ch. Tjaden, E. Soyka, M. Meinhardt; Heidelberger Stiftung Chirurgie and BMBF grant 01GS08114), the BMBH (Prof. P. Schirmacher; BMBF grant 01EY1101), the "5 x 1000" voluntary contribution of the Italian Government, the Italian Ministry of Health (RC1203GA57, RC1303GA53, RC1303GA54, RC1303GA50), the Italian Association for Research on Cancer (Prof. A. Scarpa; AIRC n. 12182), the Italian Ministry of Research (Prof. A. Scarpa; FIRB - RBAP10AHJB), the Italian FIMP-Ministry of Health (Prof. A.r Scarpa; 12 CUP_J33G13000210001), and by the National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, UK. We would like to acknowledge the contribution of Dr. Frederike Dijk and Prof. Oliver Busch (Academic Medical Center, Amsterdam, the Netherlands). Assistance with genotype data quality control was provided by Cecelia Laurie and Cathy Laurie at University of Washington Genetic Analysis Center. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort. The authors express sincere appreciation to all Cancer Prevention Study-II participants, and to each member of the study and biospecimen management group. The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention's National Program of Cancer Registries and cancer registries supported by the NCI's Surveillance Epidemiology and End Results Program. Cancer incidence data for CLUE were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene (Baltimore, MD; http://phpa.dhmh.maryland.gov/cancer; 410-767-4055). We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention for the funds that support the collection and availability of the cancer registry data." We thank Kathy J. Helzlsouer for her contribution in CLUE. We also thank all the CLUE participants. The Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057, 396414, and 1074383 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. The NYU Women's Health Study (AZJ and AAA) was funded by NIH UM1 CA182934 and center grants P30 CA016087 and P30 ES000260. The PANKRAS II Study in Spain was supported by research grants from Instituto de Salud Carlos III-FEDER, Spain; Fondo de Investigaciones Sanitarias (FIS; #PI13/00082 and #PI15/01573) and Red Tematica de Investigacion Cooperativa en Cancer, Spain (#RD12/0036/0050); and European Cooperation in Science and Technology (COST Action #BM1204: EU_Pancreas), Ministerio de Ciencia y Tecnologia (CICYT SAF 2000-0097), Fondo de Investigacion Sanitaria (95/0017), Madrid, Spain; Generalitat de Catalunya (CIRIT - SGR); 'Red tematica de investigacion cooperativa de centros en Cancer' (C03/10), 'Red tematica de investigacion cooperativa de centros en Epidemiologia y salud publica' (C03/09), and CIBER de Epidemiologia (CIBERESP), Madrid. The Physicians' Health Study was supported by research grants CA-097193, CA-34944, CA-40360, HL-26490, and HL-34595 from the NIH. The Women's Health Study was supported by research grants CA-047988, CA-182913, HL-043851, HL-080467, and HL-099355 from the NIH. Health Professionals Followup Study is supported by NIH grant UM1 CA167552 from the NCI. Nurses' Health Study is supported by NIH grants UM1 CA186107, P01 CA87969, and R01 CA49449 from the NCI. Multiethnic Cohort Study was supported by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973 from the NCI.r Additional support from the Hale Center for Pancreatic Cancer Research, U01 CA21017 from the NCI, and the United States Department of Defense CA130288, Lustgarten Foundation, Pancreatic Cancer Action Network, Noble Effort Fund, Peter R. Leavitt Family Fund, Wexler Family Fund, and Promises for Purple (to B.M. Wolpin); Broman Family Fund for Pancreatic Cancer Research (to K. Ng); and K07 CA222159 from the NCI, and Bob Parsons Fellowship (to A. Babic). The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: http://www.whi.org/researchers/Documents%20%20Write%20a% 20Paper/WHI%20Investigator%20Long%20List.pdf. SELECT is funded by the NCI of the NIH under Award Numbers U10 CA37429 (to C.D. Blanke), and UM1 CA182883 (to C.M. Tangen/I.M. Thompson). The authors thank the site investigators and staff and, most importantly, the participants from SELECT who donated their time to this trial. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at theNIH (http://biowulf.nih.gov).The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the NIH, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from the GTEx Portal on September 24, 2019.es_ES
dc.format.number18es_ES
dc.format.page4004es_ES
dc.format.volume80es_ES
dc.identifier.citationCancer Res . 2020 ;80(18):4004-4013es_ES
dc.identifier.doi10.1158/0008-5472.CAN-20-0447es_ES
dc.identifier.e-issn1538-7445es_ES
dc.identifier.journalCancer researches_ES
dc.identifier.pmchttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861352/
dc.identifier.pubmedID32641412es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/18190
dc.language.isoenges_ES
dc.publisherAmerican Association for Cancer Research (AACR)
dc.relation.publisherversionhttps://doi.org/10.1158/0008-5472.CAN-20-0447.es_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Carcinogénesis Epiteliales_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshGenetic Predisposition to Diseasees_ES
dc.subject.meshCarcinoma, Pancreatic Ductales_ES
dc.subject.meshCase-Control Studieses_ES
dc.subject.meshCeliac Diseasees_ES
dc.subject.meshCholangitis, Sclerosinges_ES
dc.subject.meshChronic Diseasees_ES
dc.subject.meshColitis, Ulcerativees_ES
dc.subject.meshCrohn Diseasees_ES
dc.subject.meshGenome-Wide Association Studyes_ES
dc.subject.meshHumanses_ES
dc.subject.meshInflammatory Bowel Diseaseses_ES
dc.subject.meshPancreatic Neoplasmses_ES
dc.subject.meshPancreatitis, Chronices_ES
dc.titleGenome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk.es_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
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