A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)

被引：160

作者：

Enciso-Mora, Victor ^{[1
]}

Broderick, Peter ^{[1
]}

Ma, Yussanne ^{[1
]}

Jarrett, Ruth F. ^{[2
]}

Hjalgrim, Henrik ^{[3
]}

Hemminki, Kari ^{[4
,5
]}

van den Berg, Anke ^{[6
]}

Olver, Bianca ^{[1
]}

Lloyd, Amy ^{[1
]}

Dobbins, Sara E. ^{[1
]}

Lightfoot, Tracy ^{[7
]}

van Leeuwen, Flora E. ^{[8
]}

Foersti, Asta ^{[4
]}

Diepstra, Arjan ^{[5
]}

Broeks, Annegien ^{[9
]}

Vijayakrishnan, Jayaram ^{[1
]}

Shield, Lesley ^{[2
]}

Lake, Annette ^{[2
]}

Montgomery, Dorothy ^{[2
]}

Roman, Eve ^{[7
]}

Engert, Andreas ^{[10
]}

von Strandmann, Elke Pogge ^{[10
]}

Reiners, Katrin S. ^{[10
]}

Nolte, Ilja M. ^{[11
]}

Smedby, Karin E. ^{[12
]}

Adami, Hans-Olov ^{[13
,14
]}

Russell, Nicola S. ^{[15
]}

Glimelius, Bengt ^{[16
,17
]}

Hamilton-Dutoit, Stephen ^{[18
]}

de Bruin, Marieke ^{[8
]}

Ryder, Lars P. ^{[19
]}

Molin, Daniel ^{[17
]}

Sorensen, Karina Meden ^{[20
]}

Chang, Ellen T. ^{[21
,22
]}

Taylor, Malcolm ^{[23
]}

Cooke, Rosie ^{[24
]}

Hofstra, Robert ^{[25
]}

Westers, Helga ^{[25
]}

van Wezel, Tom ^{[26
]}

van Eijk, Ronald ^{[26
]}

Ashworth, Alan ^{[27
]}

Rostgaard, Klaus ^{[3
]}

Melbye, Mads ^{[3
]}

Swerdlow, Anthony J. ^{[21
]}

Houlston, Richard S. ^{[1
]}

机构：

[1] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England

[2] Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland

[3] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark

[4] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany

[5] Lund Univ, Clin Res Ctr, Ctr Primary Hlth Care Res, Malmo, Sweden

[6] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Groningen, Netherlands

[7] Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England

[8] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands

[9] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Expt Therapy, Amsterdam, Netherlands

[10] Univ Hosp Cologne, Dept Internal Med, Cologne, Germany

[11] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Unit Genet Epidemiol & Bioinformat, Groningen, Netherlands

[12] Karolinska Univ Hosp, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden

[13] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[14] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA

[15] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Radiotherapy, Amsterdam, Netherlands

[16] Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden

[17] Uppsala Univ, Dept Oncol Radiol & Clin Immunol, Uppsala, Sweden

[18] Aarhus Univ Hosp, Inst Pathol, DK-8000 Aarhus, Denmark

[19] Univ Copenhagen Hosp, Rigshosp, Dept Clin Immunol, DK-2100 Copenhagen, Denmark

[20] Statens Serum Inst, Dept Clin Biochem, DK-2300 Copenhagen, Denmark

[21] Canc Prevent Inst Calif, Fremont, CA USA

[22] Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA USA

[23] Univ Manchester, St Marys Hosp, Sch Canc & Enabling Sci, Canc Immunogenet Grp, Manchester M13 0JH, Lancs, England

[24] Inst Canc Res, Epidemiol Sect, Sutton, Surrey, England

[25] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[26] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands

[27] Breakthrough Breast Canc Res Ctr, Inst Canc Res, London, England

来源：

NATURE GENETICS | 2010年 / 42卷 / 12期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

KAPPA-B-ALPHA; INFECTIOUS-MONONUCLEOSIS; COLORECTAL-CANCER; NEOPLASTIC-CELLS; PROSTATE-CANCER; INCREASED RISK; C-MYC; DISEASE; GENE; VARIANT;

D O I：

10.1038/ng.696

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 x 10(-8)), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 x 10(-13)) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 x 10(-8)). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 x 10(-50)). These data provide new insight into the pathogenesis of cHL.

引用

页码：1126 / +

页数：6

共 67 条

[1]

An epidemiologic study of index and family infectious mononucleosis and adult Hodgkin's disease (HD):: Evidence for a specific association with EBV+ve HD in young adults [J].

Alexander, FE ;

Lawrence, DJ ;

Freeland, J ;

Krajewski, AS ;

Angus, B ;

Taylor, GM ;

Jarrett, RF .

INTERNATIONAL JOURNAL OF CANCER, 2003, 107 (02) :298-302

[2]

AMIEL JL, 1967, HISTOCOMPATIBILITY T

[3]

A common variant associated with prostate cancer in European and African populations [J].

Amundadottir, Laufey T. ;

Sulem, Patrick ;

Gudmundsson, Julius ;

Helgason, Agnar ;

Baker, Adam ;

Agnarsson, Bjarni A. ;

Sigurdsson, Asgeir ;

Benediktsdottir, Kristrun R. ;

Cazier, Jean-Baptiste ;

Sainz, Jesus ;

Jakobsdottir, Margret ;

Kostic, Jelena ;

Magnusdottir, Droplaug N. ;

Ghosh, Shyamali ;

Agnarsson, Kari ;

Birgisdottir, Birgitta ;

Le Roux, Louise ;

Olafsdottir, Adalheidur ;

Blondal, Thorarinn ;

Andresdottir, Margret ;

Gretarsdottir, Olafia Svandis ;

Bergthorsson, Jon T. ;

Gudbjartsson, Daniel ;

Gylfason, Arnaldur ;

Thorleifsson, Gudmar ;

Manolescu, Andrei ;

Kristjansson, Kristleifur ;

Geirsson, Gudmundur ;

Isaksson, Helgi ;

Douglas, Julie ;

Johansson, Jan-Erik ;

Balter, Katarina ;

Wiklund, Fredrik ;

Montie, James E. ;

Yu, Xiaoying ;

Suarez, Brian K. ;

Ober, Carole ;

Cooney, Kathleen A. ;

Gronberg, Henrik ;

Catalona, William J. ;

Einarsson, Gudmundur V. ;

Barkardottir, Rosa B. ;

Gulcher, Jeffrey R. ;

Kong, Augustine ;

Thorsteinsdottir, Unnur ;

Stefansson, Kari .

NATURE GENETICS, 2006, 38 (06) :652-658

[4]

Expression of the T-cell transcription factors, GATA-3 and T-bet, in the neoplastic cells of Hodgkin lymphomas [J].

Atayar, Ç ;

Poppema, S ;

Blokzijl, T ;

Harms, G ;

Boot, M ;

van den Berg, A .

AMERICAN JOURNAL OF PATHOLOGY, 2005, 166 (01) :127-134

[5]

BAKKUS MHC, 1990, ONCOGENE, V5, P1359

[6]

Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma [J].

Barth, TFE ;

Martin-Subero, JI ;

Joos, S ;

Menz, CK ;

Hasel, C ;

Mechtersheimer, G ;

Parwaresch, RM ;

Lichter, P ;

Siebert, R ;

Möller, P .

BLOOD, 2003, 101 (09) :3681-3686

[7]

Pvt1-encoded microRNAs in oncogenesis [J].

Beck-Engeser, Gabriele B. ;

Lum, Amy M. ;

Huppi, Konrad ;

Caplen, Natasha J. ;

Wang, Bruce B. ;

Wabl, Matthias .

RETROVIROLOGY, 2008, 5 (1)

[8]

Broeks A, 2000, INT J RADIAT BIOL, V76, P693, DOI 10.1080/095530000138367

[9]

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[10]

Mutations in the IkBa gene in Hodgkin's disease suggest a tumour suppressor role for IκBα [J].

Cabannes, E ;

Khan, G ;

Aillet, F ;

Jarrett, RF ;

Hay, RT .

ONCOGENE, 1999, 18 (20) :3063-3070

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