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

被引：203

作者：

Klein, Alison P. ^{[1
,2
]}

Wolpin, Brian M. ^{[3
]}

Risch, Harvey A. ^{[4
]}

Stolzenberg-Solomon, Rachael Z. ^{[5
]}

Mocci, Evelina ^{[1
]}

Zhang, Mingfeng ^{[6
]}

Canzian, Federico ^{[7
]}

Childs, Erica J. ^{[1
]}

Hoskins, Jason W. ^{[6
]}

Jermusyk, Ashley ^{[6
]}

Zhong, Jun ^{[6
]}

Chen, Fei ^{[1
]}

Albanes, Demetrius ^{[5
]}

Andreotti, Gabriella ^{[5
]}

Arslan, Alan A. ^{[8
,9
,10
]}

Babic, Ana ^{[3
]}

Bamlet, William R. ^{[11
]}

Beane-Freeman, Laura ^{[5
]}

Berndt, Sonja I. ^{[5
]}

Blackford, Amanda ^{[1
]}

Borges, Michael ^{[2
]}

Borgida, Ayelet ^{[12
]}

Bracci, Paige M. ^{[13
]}

Brais, Lauren ^{[3
]}

Brennan, Paul ^{[14
]}

Brenner, Hermann ^{[15
,16
,17
]}

Bueno-de-Mesquita, Bas ^{[18
,19
,20
,21
]}

Buring, Julie ^{[22
,23
]}

Campa, Daniele ^{[24
]}

Capurso, Gabriele ^{[25
]}

Cavestro, Giulia Martina ^{[26
]}

Chaffee, Kari G. ^{[11
]}

Chung, Charles C. ^{[5
,27
]}

Cleary, Sean ^{[12
]}

Cotterchio, Michelle ^{[28
,29
]}

Dijk, Frederike ^{[30
]}

Duell, Eric J. ^{[31
]}

Foretova, Lenka ^{[32
]}

Fuchs, Charles ^{[33
]}

Funel, Niccola ^{[34
]}

Gallinger, Steven ^{[12
]}

Gaziano, J. Michael M. ^{[35
,36
]}

Gazouli, Maria ^{[37
]}

Giles, Graham G. ^{[38
,39
,40
]}

Giovannucci, Edward ^{[3
]}

Goggins, Michael ^{[2
]}

Goodman, Gary E. ^{[41
]}

Goodman, Phyllis J. ^{[42
]}

Hackert, Thilo ^{[43
]}

Haiman, Christopher ^{[44
]}

机构：

[1] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21231 USA

[2] Johns Hopkins Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21287 USA

[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[4] Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06520 USA

[5] NIH, Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[6] NIH, Natl Canc Inst, Div Canc Epidemiol & Genet, Lab Translat Genom, Bethesda, MD 20892 USA

[7] German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany

[8] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY 10016 USA

[9] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA

[10] NYU, Sch Med, Dept Environm Med, New York, NY 10016 USA

[11] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA

[12] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada

[13] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA

[14] IARC, F-69372 Lyon, France

[15] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany

[16] German Canc Res Ctr, Div Prevent Oncol, D-69120 Heidelberg, Germany

[17] Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany

[18] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, NL-3720 BA Bilthoven, Netherlands

[19] Univ Med Ctr, Dept Gastroenterol & Hepatol, NL-3584 CX Utrecht, Netherlands

[20] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England

[21] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur 50603, Malaysia

[22] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA

[23] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[24] Univ Pisa, Dept Biol, I-56126 Pisa, Italy

[25] Sapienza Univ Rome, Digest & Liver Dis Unit, I-00185 Rome, Italy

[26] Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Gastroenterol & Gastrointestinal Endoscopy Unit, I-20132 Milan, Italy

[27] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Div Canc Epidemiol & Genet, Cancer Genom Res Lab,Natl Canc Inst, Frederick, MD 21702 USA

[28] Univ Toronto, Cancer Care Ontario, Toronto, ON M5G 2L7, Canada

[29] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada

[30] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands

[31] Catalan Inst Oncol ICO, Bellvitge Biomed Res Inst IDIBELL, Canc Epidemiol Res Program, Unit Nutr & Canc, Barcelona 08908, Spain

[32] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65653, Czech Republic

[33] Yale Canc Ctr, New Haven, CT 06510 USA

[34] Univ Pisa, Dept Translat Res & New Technol Med & Surg, I-56126 Pisa, Italy

[35] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA

[36] Boston VA Healthcare Syst, Boston, MA 02132 USA

[37] Natl & Kapodistrian Univ Athens, Med Sch, Lab Biol, Dept Basic Med Sci, Athens 10679, Greece

[38] Canc Council Victoria, Cancer Epidemiol & Intelligence Div, Melbourne, Vic 3004, Australia

[39] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia

[40] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia

[41] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA

[42] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98109 USA

[43] Univ Heidelberg Hosp, Dept Gen Surg, D-69120 Heidelberg, Germany

[44] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90032 USA

[45] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77230 USA

[46] Univ Szeged, Dept Med 1, H-6725 Szeged, Hungary

[47] NIH, Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA

[48] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Radiat Oncol, Baltimore, MD 21231 USA

[49] Charles Univ Prague, Inst Publ Hlth & Prevent Med, Fac Med 2, Prague 15006 5, Czech Republic

[50] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

ASSOCIATION ANALYSES; GENE-EXPRESSION; RISK; IMPUTATION; DISEASE; PREDICTIONS; MUTATIONS; INSIGHTS; VARIANTS; DOMAIN;

D O I：

10.1038/s41467-018-02942-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 x 10(-8)). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PAN-DoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 x 10(-14)), rs2941471 at 8q21.11 (HNF4G, P = 6.60 x 10(-10)), rs4795218 at 17q12 (HNF1B, P = 1.32 x 10(-8)), and rs1517037 at 18q21.32 (GRP, P = 3.28 x 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.

引用

页数：11

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