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Cited by 268Pancreatic and Hepatic Oncology ResearchGenetic Associations and EpidemiologyCancer Genomics and Diagnostics

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

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Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J. +115 more·2018·Nature Communications
DOI 10.1038/s41467-018-02942-5PMC PMC5805680
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Abstract

Abstract In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/ TNS3 , P = 4.35 × 10 −8 ). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 ( NOC2L , P = 8.36 × 10 −14 ), rs2941471 at 8q21.11 ( HNF4G , P = 6.60 × 10 −10 ), rs4795218 at 17q12 ( HNF1B , P = 1.32 × 10 −8 ), and rs1517037 at 18q21.32 ( GRP , P = 3.28 × 10 −8 ). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

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Klein, A. P., Wolpin, B. M., Risch, H. A., Stolzenberg-Solomon, R. Z., Mocci, E., Zhang, M., Canzian, F., Childs, E. J., Hoskins, J. W., Jermusyk, A., Zhong, J., Chen, F., Albanes, D., Andreotti, G., Arslan, A. A., Babic, A., Bamlet, W. R., Beane-Freeman, L., Berndt, S. I., Blackford, A., Borges, M., Borgida, A., Bracci, P. M., Brais, L., Brennan, P., Brenner, H., Bueno-de-Mesquita, B., Buring, J., Campa, D., Capurso, G., Cavestro, G. M., Chaffee, K. G., Chung, C. C., Cleary, S., Cotterchio, M., Dijk, F., Duell, E. J., Foretova, L., Fuchs, C., Funel, N., Gallinger, S., M. Gaziano, J. M., Gazouli, M., Giles, G. G., Giovannucci, E., Goggins, M., Goodman, G. E., Goodman, P. J., Hackert, T., Haiman, C., Hartge, P., Hasan, M., Hegyi, P., Helzlsouer, K. J., Herman, J., Holcatova, I., Holly, E. A., Hoover, R., Hung, R. J., Jacobs, E. J., Jamroziak, K., Janout, V., Kaaks, R., Khaw, K.-T., Klein, E. A., Kogevinas, M., Kooperberg, C., Kulke, M. H., Kupcinskas, J., Kurtz, R. J., Laheru, D., Landi, S., Lawlor, R. T., Lee, I.-M., LeMarchand, L., Lu, L., Malats, N., Mambrini, A., Mannisto, S., Milne, R. L., Mohelníková-Duchoňová, B., Neale, R. E., Neoptolemos, J. P., Oberg, A. L., Olson, S. H., Orlow, I., Pasquali, C., Patel, A. V., Peters, U., Pezzilli, R., Porta, M., Real, F. X., Rothman, N., Scelo, G., Sesso, H. D., Severi, G., Shu, X.-O., Silverman, D., Smith, J. P., Soucek, P., Sund, M., Talar-Wojnarowska, R., Tavano, F., Thornquist, M. D., Tobias, G. S., Van Den Eeden, S. K., Vashist, Y., Visvanathan, K., Vodicka, P., Wactawski-Wende, J., Wang, Z., Wentzensen, N., White, E., Yu, H., Yu, K., Zeleniuch-Jacquotte, A., Zheng, W., Kraft, P., Li, D., Chanock, S., Obazee, O., Petersen, G. M., & Amundadottir, L. T.
Affiliations
  • Johns Hopkins University (US)
  • Dana-Farber Cancer Institute (US)
  • Yale University (US)
  • National Institutes of Health (US)
  • German Cancer Research Center (DE)
  • New York University (US)
  • Mayo Clinic (US)
  • Mount Sinai Hospital (CA)
  • University of California, San Francisco (US)
  • Centre international de recherche sur le cancer (FR)
  • University Medical Center Utrecht (NL)
  • Brigham and Women's Hospital (US)
  • University of Pisa (IT)
  • Sapienza University of Rome (IT)
  • Vita-Salute San Raffaele University (IT)
  • University of Toronto (CA)
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Institut d'Investigació Biomédica de Bellvitge (ES)
  • Yale Cancer Center (US)
  • National and Kapodistrian University of Athens (GR)
  • The University of Melbourne (AU)
  • Fred Hutch Cancer Center (US)
  • University Hospital Heidelberg (DE)
  • University of Southern California (US)
  • The University of Texas MD Anderson Cancer Center (US)
  • American Cancer Society (US)
  • Instytut Hematologii i Transfuzjologi (PL)
  • University of Cambridge (GB)
  • Cleveland Clinic (US)
  • Universitat Autònoma de Barcelona (ES)
  • Memorial Sloan Kettering Cancer Center (US)
  • University of Verona (IT)
  • Spanish National Cancer Research Centre (ES)
  • University Hospital Olomouc (CZ)
  • Heidelberg University (DE)
  • University of Padua (IT)
  • IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
  • Universitat Pompeu Fabra (ES)
  • Inserm (FR)
  • Vanderbilt University (US)
  • Georgetown University (US)
  • Umeå University (SE)
  • Casa Sollievo della Sofferenza (IT)
  • Universität Hamburg (DE)
  • St. Jude Children's Research Hospital (US)
  • University of Washington (US)
  • University of Hawaii Cancer Center (US)
  • Harvard University (US)
Corresponding author
  • Klein, Alison P.
  • Amundadottir, Laufey T.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-02-08
Volume
9
Issue
1
Pages
556-556
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-02942-5
PMC
PMC5805680
OpenAlex
W2788540749
Cited by
268
References
11
Citations by year
2026: 19 · 2025: 26 · 2024: 28 · 2023: 52 · 2022: 37 · 2021: 40 · 2020: 37 · 2019: 22 · 2018: 7
FWCI
2.95
Type
journal article
Language
en
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  • U.S. Department of Defense (UM1 CA186107, P30 CA016087, CA130288, P01 CA87969, R01 CA49449)
  • U.S. Department of Health and Human Services (P30 CA008748, HHSN268201600002 C, HHSN268201600018 C, UM1 CA186107, HHSN268201600003C, R01CA49449, HHSN261200800001E, P01 CA87969, ES000260, HSN261201000140C, HHSN268201600004 C, HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C, CA016087, HHSN268201600001 C)
  • American Cancer Society (CA49449, P30CA008748, CA87969)
  • Mayo Clinic (CA102701, P30CA008748, P50 CA102701, HHSN261200800001E)
  • Pancreatic Cancer Action Network
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  • State of Connecticut Department of Public Health
  • New York City Department of Health and Mental Hygiene
  • California Department of Public Health (UM1 CA186107, U58DP003862-01, 209057, P01 CA87969, HSN261201000140C, 396414)
  • Yale University
  • Kaiser Permanente
  • Lustgarten Foundation
  • Memorial Sloan-Kettering Cancer Center (P30 CA008748, RO1CA102765)
  • University of Washington (HHSN261200800001E)
  • Johns Hopkins University (P50CA062924, R01CA97075, HHSN268201100011I)
  • Geoffrey Beene Foundation
  • Fondazione Italiana per la ricerca sulle Malattie del Pancreas
  • Cancer Research UK (14136)
  • National Institute for Health and Care Research (P01 CA87969, R01 CA49449, 209057, UM1 CA167552, 396414, UM1 CA186107, NF-SI-0512-10114)
  • Grantová Agentura České Republiky (00209805), GAP301/12/1734)
  • Bundesministerium für Bildung und Forschung (UM1 CA186107, 01EY1101, P01 CA87969, 396414, 01GS08114, 209057, UM1 CA167552)
  • Generalitat de Catalunya
  • Ministero della Salute (RC1303GA54, “5×1000”, RC1303GA50, CUPJ33G13000210001, 12 CUP_J33G13000210001, RC1303GA53)
  • Ministerstvo Zdravotnictví Ceské Republiky (MMCI, 00209805, 00209805), MH CZ-DRO-MMCI 00209805, NR 9029-4/2006, NR9422-3, NR9998-3, 9029-4)
  • Associazione Italiana per la Ricerca sul Cancro (n. 12182, 5×1000, 12182, P01 CA87969, 396414, 209057, UM1 CA186107)
  • Ministerio de Ciencia y Tecnología (2000-0097, CICYT SAF 2000-0097)
  • National Institutes of Health (CA 34944, R01CA1009767, HHSN268201600018C, 5r01ca049449-19, 5r01ca098870-06, #HHSN261200800001E, 1r03ca123546-01, HHSN268201600003C, CA130288, HHSN268201600004C, NIH-R01, HHSN261200800001C, HHSN268201600001C, 5r01hl043851-10, 209057, HHSN268201600002C, 396414, R01 CA49449, CA-49449, UM1-CA167552, R03 CA123546-02, HL-043851, CA016087, CA 40360, CA-167552, R01CA109767-S1, CA102701, CA186107, UM1 CA186107, P01 CA87969, and R01 CA49449, ES000260, CA 87969, 5R01CA098870, R0CA059706, UL1TR001863, HL-26490)
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  • Cancer Council Victoria (UM1 CA186107, 209057, P01 CA87969, 396414)
  • Instituto de Salud Carlos III (C03/09, PI13/00082, BM1204: EU_Pancreas, PI15/01573)
  • National Heart, Lung, and Blood Institute (R01HL080467, HL-34595, HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C and HHSN268201600004C, CA-40360, HL043851, HHSN268201100011C, HHSN268201600018C, HL 26490, R01‐HL043851, HL099355, HHSN268201600004C, CA-34944, HHSN268201600001C, CA186107, HHSN268201100011I, R01 HL026490, HHSN261200800001E, RC1HL099355, HL080467, CA167552, R01HL034595, CA 097193, CA49449, contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C, HHSN268201600003C, CA047988, NIH R01, CA87969, HHSN268201600002C)
  • National Institute of Mental Health (HHSN261200800001E)
  • National Institute on Drug Abuse
  • National Human Genome Research Institute (HHSN261200800001E)
  • NIH Office of the Director (HHSN261200800001E, ES000260, P30CA008748)
  • National Cancer Institute (HL-080467, HL-099355, CA-167552, R01CA040360, CA-49449, HSN261201000140C, R01 CA109767-S1, CA130288, CA102701, ES 000260, R01 CA098870, R01CA-97075, CA 016087, HHSN268201600018C, HHSN268201600001C, CA-87969, HL 26490, UM1CA182883, R01CA109767, HL-043851, R01CA154823, UG1CA189974, R01-CA49449, U01CA167462, R01 CA1009767, HHSN261200800001E), UM1CA182934, P01CA087969, 5R01CA098870, R01CA098661, CA 34944, U01CA074783, HHSN268201600002C, CA154823, CA-186107, HHSN268201600003C, R01 CA034944, R01‐CA049449, CA-097193, 209057, 396414, R01CA097193, HL-34595, P50CA102701, CA 047988, R01CA102765, CA 40360, UM1CA167462, RO1 CA154823, U24CA074783, R01CA097075, R03 CA123546, HHSN268201600004C, UM1CA186107, R03 CA123546-02, R0CA059706, U10CA037429, R01CA047988, UM1CA167552, U01 CA21017, U58DP003862-01, P50CA062924, [P01 CA87969, P30CA008748, U01CA167551, U01CA210171, P30CA016087, U01CA167552, CA098661)
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Environmental Health Sciences (P30ES000260)
  • National Center for Chronic Disease Prevention and Health Promotion (U58 DP003862)
  • National Center for Advancing Translational Sciences
  • Common Fund (UM1 CA186107, P30 CA008748, R01 CA49449)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
pancreatic cancer, genetic susceptibility loci, common genetic variants, HNF4G, HNF1B, GRP, expression quantitative trait loci, Pandora, European ancestry
MeSH terms
Tensins, Humans, Pancreatic Neoplasms, Proteins, Repressor Proteins, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Carcinoma, Pancreatic Ductal, Databases, Genetic, Intercellular Signaling Peptides and Proteins, Intracellular Signaling Peptides and Proteins, Hepatocyte Nuclear Factor 1-beta, Hepatocyte Nuclear Factor 4, Genome-Wide Association Study

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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