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A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus

W. Cozen (), M. N. Timofeeva, D. Li, A. Diepstra, D. Hazelett, M. Delahaye-Sourdeix, C. K. Edlund, L. Franke, K. Rostgaard, D. J. Van Den Berg, V. K. Cortessis, K. E. Smedby, S. L. Glaser, H.-J. Westra, L. L. Robison, T. M. Mack, H. Ghesquieres, A. E. Hwang, A. Nieters, S. de Sanjose, T. Lightfoot, N. Becker, M. Maynadie, L. Foretova, E. Roman, Y. Benavente, K. A. Rand, B. N. Nathwani, B. Glimelius, A. Staines, P. Boffetta, B. K. Link, L. Kiemeney, S. M. Ansell, S. Bhatia, L. C. Strong, P. Galan, L. Vatten, T. M. Habermann, E. J. Duell, A. Lake, R. N. Veenstra, L. Visser, Y. Liu, K. Y. Urayama, D. Montgomery, V. Gaborieau, L. M. Weiss, G. Byrnes, M. Lathrop, P. Cocco, T. Best, A. D. Skol, H.-O. Adami, M. Melbye, J. R. Cerhan, A. Gallagher, G. M. Taylor, S. L. Slager, P. Brennan, G. A. Coetzee, D. V. Conti, K. Onel, R. F. Jarrett, H. Hjalgrim, A. van den Berg () and J. D. McKay ()
Additional contact information
W. Cozen: USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California
M. N. Timofeeva: International Agency for Research on Cancer (IARC)
A. Diepstra: University of Groningen, University Medical Centre Groningen
D. Hazelett: USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California
M. Delahaye-Sourdeix: International Agency for Research on Cancer (IARC)
C. K. Edlund: USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California
L. Franke: University of Groningen, University Medical Centre Groningen
K. Rostgaard: Statens Serum Institut
D. J. Van Den Berg: USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California
V. K. Cortessis: USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California
K. E. Smedby: Karolinska Institutet and Karolinska University Hospital
S. L. Glaser: Cancer Prevention Institute of California
H.-J. Westra: University of Groningen, University Medical Centre Groningen
L. L. Robison: St Jude Children’s Hospital
T. M. Mack: USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California
H. Ghesquieres: Centre Léon Bérard, UMR CNRS 5239–Université Lyon 1
A. E. Hwang: USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California
A. Nieters: University Medical Centre Freiburg
S. de Sanjose: IDIBELL Institut Català d'Oncologia
T. Lightfoot: University of York
N. Becker: German Cancer Research Centre
M. Maynadie: CHU de Dijon, EA 4184, University of Burgundy
L. Foretova: Masaryk Memorial Cancer Institute
E. Roman: University of York
Y. Benavente: IDIBELL Institut Català d'Oncologia
K. A. Rand: USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California
B. N. Nathwani: City of Hope National Medical Center
B. Glimelius: Uppsala University
A. Staines: School of Nursing and Human Sciences, Dublin City University, Glasnevin
P. Boffetta: Icahn School of Medicine at Mount Sinai
B. K. Link: University of Iowa College of Medicine
L. Kiemeney: Radboud University Nijmegen Medical Centre
S. M. Ansell: Mayo Clinic
S. Bhatia: City of Hope National Medical Center
L. C. Strong: MD Anderson Cancer Center, University of Texas
P. Galan: INSERM U557 (UMR Inserm; INRA; CNAM, Université Paris 13)
L. Vatten: Norwegian University of Science and Technology
T. M. Habermann: Mayo Clinic
E. J. Duell: IDIBELL Institut Català d'Oncologia
A. Lake: MRC University of Glasgow Centre for Virus Research, Garscube Estate, University of Glasgow
R. N. Veenstra: University of Groningen, University Medical Centre Groningen
L. Visser: University of Groningen, University Medical Centre Groningen
Y. Liu: University of Groningen, University Medical Centre Groningen
K. Y. Urayama: Tokyo Medical and Dental University
D. Montgomery: MRC University of Glasgow Centre for Virus Research, Garscube Estate, University of Glasgow
V. Gaborieau: International Agency for Research on Cancer (IARC)
L. M. Weiss: Clarient Pathology Services
G. Byrnes: International Agency for Research on Cancer (IARC)
M. Lathrop: Genome Quebec
P. Cocco: Institute of Occupational Health, University of Cagliari, Monserrato
T. Best: The University of Chicago
A. D. Skol: The University of Chicago
H.-O. Adami: Karolinska Institutet and Karolinska University Hospital
M. Melbye: Statens Serum Institut
J. R. Cerhan: Mayo Clinic
A. Gallagher: MRC University of Glasgow Centre for Virus Research, Garscube Estate, University of Glasgow
G. M. Taylor: School of Cancer Sciences, University of Manchester, St Mary’s Hospital
S. L. Slager: Mayo Clinic
P. Brennan: International Agency for Research on Cancer (IARC)
G. A. Coetzee: USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California
D. V. Conti: USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California
K. Onel: The University of Chicago
R. F. Jarrett: MRC University of Glasgow Centre for Virus Research, Garscube Estate, University of Glasgow
H. Hjalgrim: Statens Serum Institut
A. van den Berg: University of Groningen, University Medical Centre Groningen
J. D. McKay: International Agency for Research on Cancer (IARC)

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI)=0.76–0.86, Pcombined=3.5 × 10−10), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4856

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DOI: 10.1038/ncomms4856

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