Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

Nature Genetics

Volumn 46, Issue 9, 2014, Pages 994-1000

  Wolpin, Brian M ^a,b   Rizzato, Cosmeri ^c   Kraft, Peter ^d   Kooperberg, Charles ^e   Petersen, Gloria M ^f   Wang, Zhaoming ^g,h   Arslan, Alan A ^i,j   Beane Freeman, Laura ^g   Bracci, Paige M ^k   Buring, Julie ^b   Canzian, Federico ^c   Duell, Eric J ^m   Gallinger, Steven ⁿ   Giles, Graham G ^o,p,q   Goodman, Gary E ^e   Goodman, Phyllis J ^r   Jacobs, Eric J ^s   Kamineni, Aruna ^t   Klein, Alison P ^u,v   Kolonel, Laurence N ^w   Kulke, Matthew H ^a   Li, Donghui ^x   Malats, Núria ^y   Olson, Sara H ^z   Risch, Harvey A ^aa   Sesso, Howard D ^b,d,l   Visvanathan, Kala ^v   White, Emily ^e,ab   Zheng, Wei ^ac,ad   Abnet, Christian C ^g   Albanes, Demetrius ^g   Andreotti, Gabriella ^g   Austin, Melissa A ^ab   Barfield, Richard ^d   Basso, Daniela ^ae   Berndt, Sonja I ^g   Boutron Ruault, Marie Christine ^af,ag   Brotzman, Michelle ^ah   Büchler, Markus W ^ai   Bueno De Mesquita, H Bas ^aj,ak   Bugert, Peter ^al   Burdette, Laurie ^g,h   Campa, Daniele ^c   Caporaso, Neil E ^g   Capurso, Gabriele ^am   Chung, Charles ^g,h   Cotterchio, Michelle ^an   Costello, Eithne ^ao   Elena, Joanne ^g   Funel, Niccola ^ap   Gaziano, J Michael ^b,l,aq   Giese, Nathalia A ^ai   Giovannucci, Edward L ^d,ar   Goggins, Michael ^u,as   Gorman, Megan J ^a   Gross, Myron ^at   Haiman, Christopher A ^au   Hassan, Manal ^x   Helzlsouer, Kathy J ^av   Henderson, Brian E ^au   Holly, Elizabeth A ^k   Hu, Nan ^g   Hunter, David J ^b,d,ar   Innocenti, Federico ^aw   Jenab, Mazda ^ax   Kaaks, Rudolf ^c   Key, Timothy J ^ay   Khaw, Kay Tee ^az   Klein, Eric A ^ba   Kogevinas, Manolis ^bb,bc,bd   Krogh, Vittorio ^be   Kupcinskas, Juozas ^bf   Kurtz, Robert C ^z   Lacroix, Andrea ^e   Landi, Maria T ^g   Landi, Stefano ^bg   Le Marchand, Loic ^w   Mambrini, Andrea ^bh   Mannisto, Satu ^bi   Milne, Roger L ^o,p   Nakamura, Yusuke ^bj   Oberg, Ann L ^f   Owzar, Kouros ^bk   Patel, Alpa V ^s   Peeters, Petra H M ^ak,bl   Peters, Ulrike ^e   Pezzilli, Raffaele ^bm   Piepoli, Ada ^bn   Porta, Miquel ^bc,bo,bp   Real, Francisco X ^y,bq   Riboli, Elio ^bl   Rothman, Nathaniel ^g   Scarpa, Aldo ^br   Shu, Xiao Ou ^ac,ad   Silverman, Debra T ^g   Soucek, Pavel ^bs   Sund, Malin ^bt   Talar Wojnarowska, Renata ^bu   Taylor, Philip R ^g   Theodoropoulos, George E ^bv   Thornquist, Mark ^e   Tjønneland, Anne ^bw   Tobias, Geoffrey S ^g   Trichopoulos, Dimitrios ^d,bx,by   Vodicka, Pavel ^bz   Wactawski Wende, Jean ^l   Wentzensen, Nicolas ^g   Wu, Chen ^d   Yu, Herbert ^w   Yu, Kai ^g   Zeleniuch Jacquotte, Anne ^i,j   Hoover, Robert ^g   Hartge, Patricia ^g   Fuchs, Charles ^a,ar   Chanock, Stephen J ^g,h   Stolzenberg Solomon, Rachael S ^g   Amundadottir, Laufey T ^g   more..

^a DANA FARBER CANCER INSTITUTE   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^d HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^e Fred Hutchinson Cancer Research Center   (United States)

^f MAYO CLINIC   (United States)

^g NATIONAL CANCER INSTITUTE   (United States)

^h NATIONAL CANCER INSTITUTE   (United States)

ⁱ NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^j NEW YORK UNIVERSITY   (United States)

^k UNIVERSITY OF CALIFORNIA   (United States)

^l UNIVERSITY AT BUFFALO   (United States)

^m BELLVITGE BIOMEDICAL RESEARCH INSTITUTE IDIBELL   (Spain)

ⁿ MOUNT SINAI HOSPITAL   (Canada)

^o CANCER EPIDEMIOLOGY CENTRE   (Australia)

^p UNIVERSITY OF MELBOURNE   (Australia)

^q MONASH UNIVERSITY   (Australia)

^r SOUTHWEST ONCOLOGY GROUP STATISTICAL CENTER   (United States)

^s AMERICAN CANCER SOCIETY   (United States)

^t GROUP HEALTH RESEARCH INSTITUTE   (United States)

^u JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^v JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

^w UNIVERSITY OF HAWAII CANCER CENTER   (United States)

^x UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^y Centro Nacional de Investigaciones Oncológicas   (Spain)

^z MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^aa YALE UNIVERSITY   (United States)

^ab UNIVERSITY OF WASHINGTON   (United States)

^ac VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^ad VANDERBILT INGRAM CANCER CENTER   (United States)

^ae UNIVERSITY HOSPITAL OF PADOVA   (Italy)

^af CENTRE FOR RESEARCH IN EPIDEMIOLOGY AND POPULATION HEALTH   (France)

^ag INSTITUT GUSTAVE ROUSSY   (France)

^ah WESTAT   (United States)

^ai UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^aj NATIONAL INSTITUTE FOR PUBLIC HEALTH AND THE ENVIRONMENT   (Netherlands)

^ak UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^al MEDICAL FACULTY MANNHEIM HEIDELBERG UNIVERSITY   (Germany)

^am SAPIENZA UNIVERSITY OF ROME   (Italy)

^an UNIVERSITY OF TORONTO   (Canada)

^ao Department of General Surgery University Hospital Heidelberg ^*  (United Kingdom)

^ap UNIVERSITY HOSPITAL OF PISA   (Italy)

^aq VETERANS AFFAIRS MEDICAL CENTER   (United States)

^ar HARVARD MEDICAL SCHOOL   (United States)

^as JOHNS HOPKINS UNIVERSITY   (United States)

^at UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^au UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^av MERCY MEDICAL CENTER   (United States)

^aw UNIVERSITY OF NORTH CAROLINA   (United States)

^ax INTERNATIONAL AGENCY FOR RESEARCH ON CANCER   (France)

^ay UNIVERSITY OF OXFORD   (United Kingdom)

^az UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^ba LERNER RESEARCH INSTITUTE   (United States)

^bb CENTRE FOR RESEARCH IN ENVIRONMENTAL EPIDEMIOLOGY CREAL   (Spain)

^bc HOSPITAL DEL MAR   (Spain)

^bd NATIONAL SCHOOL OF PUBLIC HEALTH   (Greece)

^be NATIONAL CANCER INSTITUTE   (Italy)

^bf LITHUANIAN UNIVERSITY OF HEALTH SCIENCES   (Lithuania)

^bg UNIVERSITY OF PISA   (Italy)

^bh ASL1 Massa Carrara   (Italy)

^bi NATIONAL PUBLIC HEALTH INSTITUTE   (Finland)

^bj UNIVERSITY OF TOKYO   (Japan)

^bk DUKE UNIVERSITY MEDICAL CENTER   (United States)

^bl IMPERIAL COLLEGE LONDON   (United Kingdom)

^bm UNIVERSITY OF BOLOGNA   (Italy)

^bn CASA SOLLIEVO DELLA SOFFERENZA HOSPITAL   (Italy)

^bo UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^bp CIBER EPIDEMIOLOGÍA Y SALUD PÚBLICA CIBERESP   (Spain)

^bq UNIVERSITAT POMPEU FABRA   (Spain)

^br ARC NET Center for Applied Research on Cancer   (Italy)

^bs NATIONAL INSTITUTE OF PUBLIC HEALTH   (Czech Republic)

^bt UMEÅ UNIVERSITY   (Sweden)

^bu MEDICAL UNIVERSITY OF LODZ   (Poland)

^bv HIPPOKRATION HOSPITAL   (Greece)

^bw INSTITUTE OF CANCER EPIDEMIOLOGY   (Denmark)

^bx BIOMEDICAL RESEARCH FOUNDATION   (Greece)

^by HELLENIC HEALTH FOUNDATION   (Greece)

^bz INSTITUTE OF EXPERIMENTAL MEDICINE   (Czech Republic)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ATM PROTEIN; CHYMOTRYPSINOGEN; CLPTM1L PROTEIN; CRK ASSOCIATED SUBSTRATE PROTEIN; CTRB1 PROTEIN; CTRB2 PROTEIN; LINC PINT PROTEIN; PEPTIDES AND PROTEINS; PROTEIN P53; PVT1 PROTEIN; TELOMERASE REVERSE TRANSCRIPTASE; TRANSCRIPTION FACTOR PDX 1; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; VON WILLEBRAND FACTOR CLEAVING PROTEINASE; ZNRF3 PROTEIN;

ADULT; AGED; ARTICLE; CANCER RISK; CASE CONTROL STUDY; CELL ADHESION; CELL CYCLE REGULATION; CELL MIGRATION; CHROMOSOME 13Q; CONTROLLED STUDY; CYTOSKELETON; ENZYME ACTIVE SITE; EXON; EXTRACELLULAR MATRIX; FEMALE; FOLLOW UP; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENE MAPPING; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETIC SUSCEPTIBILITY; GENETIC TRANSCRIPTION; GENOTYPE; HUMAN; MAJOR CLINICAL STUDY; MALE; META ANALYSIS; PANCREAS CANCER; PHENOTYPE; PRIORITY JOURNAL; PROMOTER REGION; QUANTITATIVE TRAIT LOCUS; SINGLE NUCLEOTIDE POLYMORPHISM; WNT SIGNALING PATHWAY; CAUCASIAN; GENETICS; GENOME-WIDE ASSOCIATION STUDY; MIDDLE AGED; PANCREAS TUMOR; PROCEDURES;

AGED; CASE-CONTROL STUDIES; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; MALE; MIDDLE AGED; PANCREATIC NEOPLASMS; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84938423709     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3052     Document Type: Article

References (53)

1. Siegel, R., Ma, J., Zou, Z. & Jemal, A. Cancer statistics, 2014. CA Cancer J. Clin. 64, 9-29 (2014
2. Ferlay, J. et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur. J. Cancer 49, 1374-1403 (2013
3. Hidalgo, M. Pancreatic cancer. N. Engl. J. Med. 362, 1605-1617 (2010
4. Klein, A.P. Genetic susceptibility to pancreatic cancer. Mol. Carcinog. 51, 14-24 (2012
5. Amundadottir, L. et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat. Genet. 41, 986-990 (2009
6. Petersen, G.M. et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat. Genet. 42, 224-228 (2010
7. Wu, C. et al. Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Nat. Genet. 44, 62-66 (2012
8. Low, S.K. et al. Genome-wide association study of pancreatic cancer in Japanese population. PLoS ONE 5, e11824 (2010
9. Wang, Z. et al. Improved imputation of common and uncommon SNPs with a new reference set. Nat. Genet. 44, 6-7 (2012
10. Campa, D. et al. Genetic susceptibility to pancreatic cancer and its functional characterisation: the PANcreatic Disease ReseArch (PANDoRA) consortium. Dig. Liver Dis. 45, 95-99 (2013
11. Innocenti, F. et al. A genome-wide association study of overall survival in pancreatic cancer patients treated with gemcitabine in CALGB 80303. Clin. Cancer Res. 18, 577-584 (2012
12. Adams, J.C., Seed, B. & Lawler, J. Muskelin, a novel intracellular mediator of cell adhesive and cytoskeletal responses to thrombospondin-1. EMBO J. 17, 4964-4974 (1998
13. Fernandez-Zapico, M.E. et al. A functional family-wide screening of SP/KLF proteins identifies a subset of suppressors of KRAS-mediated cell growth. Biochem. J. 435, 529-537 (2011
14. Small, K.S. et al. Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes. Nat. Genet. 43, 561-564 (2011
15. Barrett, A., Pellet-Many, C., Zachary, I.C., Evans, I.M. & Frankel, P. p130Cas: a key signalling node in health and disease. Cell. Signal. 25, 766-777 (2013
16. Cabodi, S., del Pilar Camacho-Leal, M., Di Stefano, P. & Defilippi, P. Integrin signalling adaptors: not only figurants in the cancer story. Nat. Rev. Cancer 10, 858-870 (2010
17. Whitcomb, D.C. & Lowe, M.E. Human pancreatic digestive enzymes. Dig. Dis. Sci. 52, 1-17 (2007
18. Whitcomb, D.C. Genetic aspects of pancreatitis. Annu. Rev. Med. 61, 413-424 (2010
19. Chen, J.M. & Ferec, C. Chronic pancreatitis: genetics and pathogenesis. Annu. Rev. Genomics Hum. Genet. 10, 63-87 (2009
20. Barrett, J.C. et al. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat. Genet. 41, 703-707 (2009
21. Morris, A.P. et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat. Genet. 44, 981-990 (2012
22. Harder, M.N. et al. Type 2 diabetes risk alleles near BCAR1 and in ANK1 associate with decreased beta-cell function whereas risk alleles near ANKRD55 and GRB14 associate with decreased insulin sensitivity in the Danish Inter99 cohort. J. Clin. Endocrinol. Metab. 98, E801-E806 (2013
23. Hart, L.M. et al. The CTRB1/2 locus affects diabetes susceptibility and treatment via the incretin pathway. Diabetes 62, 3275-3281 (2013
24. Stoffers, D.A., Zinkin, N.T., Stanojevic, V., Clarke, W.L. & Habener, J.F. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat. Genet. 15, 106-110 (1997
25. MacDonald, R.J., Swift, G.H. & Real, F.X. Transcriptional control of acinar development and homeostasis. Prog. Mol. Biol. Transl. Sci. 97, 1-40 (2010
26. Vaxillaire, M., Bonnefond, A. & Froguel, P. The lessons of early-onset monogenic diabetes for the understanding of diabetes pathogenesis. Best Pract. Res. Clin. Endocrinol. Metab. 26, 171-187 (2012
27. Ohlsson, H., Karlsson, K. & Edlund, T. IPF1, a homeodomain-containing transactivator of the insulin gene. EMBO J. 12, 4251-4259 (1993
28. Manning, A.K. et al. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat. Genet. 44, 659-669 (2012
29. Hao, H.X. et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature 485, 195-200 (2012
30. Antoni, L., Sodha, N., Collins, I. & Garrett, M.D. CHK2 kinase: cancer susceptibility and cancer therapy-two sides of the same coin?. Nat. Rev. Cancer 7, 925-936 (2007
31. Gronwald, J. et al. Cancer risks in first-degree relatives of CHEK2 mutation carriers: effects of mutation type and cancer site in proband. Br. J. Cancer 100, 1508-1512 (2009
32. Fearnhead, P. SequenceLDhot: detecting recombination hotspots. Bioinformatics 22, 3061-3066 (2006
33. Ballew, B.J. & Savage, S.A. Updates on the biology and management of dyskeratosis congenita and related telomere biology disorders. Expert Rev. Hematol. 6, 327-337 (2013
34. Horn, S. et al. TERT promoter mutations in familial and sporadic melanoma. Science 339, 959-961 (2013
35. James, M.A., Vikis, H.G., Tate, E., Rymaszewski, A.L. & You, M. CRR9/CLPTM1L regulates cell survival signaling and is required for Ras transformation and lung tumorigenesis. Cancer Res. 74, 1116-1127 (2014
36. Jia, J. et al. CLPTM1L promotes growth and enhances aneuploidy in pancreatic cancer cells. Cancer Res. 74, 2785-2795 (2014
37. Rafnar, T. et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat. Genet. 41, 221-227 (2009
38. Speedy, H.E. et al. A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia. Nat. Genet. 46, 56-60 (2014
39. McKay, J.D. et al. Lung cancer susceptibility locus at 5p15.33. Nat. Genet. 40, 1404-1406 (2008
40. Bojesen, S.E. et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat. Genet. 45, 371-384 (2013
41. Kote-Jarai, Z. et al. Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression. Hum. Mol. Genet. 22, 2520-2528 (2013
42. Grisanzio, C. & Freedman, M.L. Chromosome 8q24-associated cancers and MYC. Genes Cancer 1, 555-559 (2010
43. Huppi, K., Pitt, J.J., Wahlberg, B.M. & Caplen, N.J. The 8q24 gene desert: an oasis of non-coding transcriptional activity. Front. Genet. 3, 69 (2012
44. Pharoah, P.D. et al. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nat. Genet. 45, 362-370 (2013
45. Ahmadiyeh, N. et al. 8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC. Proc. Natl. Acad. Sci. USA 107, 9742-9746 (2010
46. Meyer, K.B. et al. A functional variant at a prostate cancer predisposition locus at 8q24 is associated with PVT1 expression. PLoS Genet. 7, e1002165 (2011
47. Ward, L.D. & Kellis, M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res. 40, D930-D934 (2012
48. Grundberg, E. et al. Mapping cis- and trans-regulatory effects across multiple tissues in twins. Nat. Genet. 44, 1084-1089 (2012
49. Yang, T.P. et al. Genevar: a database and Java application for the analysis and visualization of SNP-gene associations in eQTL studies. Bioinformatics 26, 2474-2476 (2010
50. Westra, H.J. et al. Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat. Genet. 45, 1238-1243 (2013
51. Lee, A.H., Heidtman, K., Hotamisligil, G.S. & Glimcher, L.H. Dual and opposing roles of the unfolded protein response regulated by IRE1? and XBP1 in proinsulin processing and insulin secretion. Proc. Natl. Acad. Sci. USA 108, 8885-8890 (2011
52. Tabas-Madrid, D., Nogales-Cadenas, R. & Pascual-Montano, A. GeneCodis3: a non-redundant and modular enrichment analysis tool for functional genomics. Nucleic Acids Res. 40, W478-W483 (2012
53. Yang, J., Lee, S.H., Goddard, M.E. & Visscher, P.M. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76-82 (2011