Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma

被引：17

作者：

Sud, Amit ^{[1
]}

Thomsen, Hauke ^{[2
]}

Orlando, Giulia ^{[1
]}

Foersti, Asta ^{[2
,3
]}

Law, Philip J. ^{[1
]}

Broderick, Peter ^{[1
]}

Cooke, Rosie ^{[1
]}

Hariri, Fadi ^{[4
,5
]}

Pastinen, Tomi ^{[4
,5
]}

Easton, Douglas F. ^{[6
,7
]}

Pharoah, Paul D. P. ^{[6
,7
]}

Dunning, Alison M. ^{[6
]}

Peto, Julian ^{[8
]}

Canzian, Federico ^{[9
]}

Eeles, Rosalind ^{[1
,10
]}

Kote-Jarai, ZSofia ^{[1
]}

Muir, Kenneth ^{[11
,12
]}

Pashayan, Nora ^{[7
,13
]}

Campa, Daniele ^{[14
]}

Hoffmann, Per ^{[15
,16
,17
]}

Noethen, Markus M. ^{[16
,17
]}

Joeckel, Karl-Heinz ^{[18
]}

von Strandmann, Elke Pogge ^{[19
]}

Swerdlow, Anthony J. ^{[1
,20
]}

Engert, Andreas ^{[21
]}

Orr, Nick ^{[20
]}

Hemminki, Kari ^{[2
,3
]}

Houlston, Richard S. ^{[1
]}

机构：

[1] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England

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

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

[4] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[5] McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ, Canada

[6] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England

[7] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England

[8] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London, England

[9] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany

[10] Royal Marsden NHS Fdn Trust, London, England

[11] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England

[12] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry, W Midlands, England

[13] UCL, Dept Appl Hlth Res, London, England

[14] Univ Pisa, Dept Biol, Pisa, Italy

[15] Univ Basel, Dept Biomed, Human Genom Res Grp, Basel, Switzerland

[16] Univ Bonn, Life & Brain Ctr, Inst Human Genet, Bonn, Germany

[17] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany

[18] Univ Duisburg Essen, Essen, Germany

[19] Philipps Univ, Ctr Tumor Biol & Immunol, Clin Hematol Oncol & Immunol, Expt Tumor Res, Marburg, Germany

[20] Inst Canc Res, Div Breast Canc Res, London, England

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

来源：

BLOOD | 2018年 / 132卷 / 19期

基金：

英国医学研究理事会; 英国惠康基金; 加拿大健康研究院; 美国国家卫生研究院;

关键词：

REED-STERNBERG CELLS; CENTER B-CELL; TRANSCRIPTION FACTOR; TARGET GENE; C-MYC; EXPRESSION; RECEPTOR; DISEASE; PROTEIN; RISK;

D O I：

10.1182/blood-2018-06-855296

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

To further our understanding of inherited susceptibility to Hodgkin lymphoma (HL), we performed a meta-analysis of 7 genome-wide association studies totaling 5325 HL cases and 22 423 control patients. We identify 5 new HL risk loci at 6p21.31 (rs649775; P = 2.11 x 10(9), 6q23.3 (rs1002658; P = 2.97 x 10(-8)), 11q23.1 (rs7111520; P = 1.44 x 10(-11)), 16p11.2 (rs6565176; P = 4.00 x 10(-8)), and 20q13.12 (rs2425752; P = 2.01 x 10(-8)). Integration of gene expression, histone modification, and in situ promoter capture Hi-C data at the 5 new and 13 known risk loci implicates dysfunction of the germinal center reaction, disrupted T-cell differentiation and function, and constitutive NF-kappa B activation as mechanisms of predisposition. These data provide further insights into the genetic susceptibility and biology of HL.

引用

页码：2040 / 2052

页数：13

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