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Nat Commun. 2014 Jun 12;5:3856. doi: 10.1038/ncomms4856.

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

Author information

1
1] USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089-9175, USA [2].
2
1] International Agency for Research on Cancer (IARC), 69372 Lyon, France [2] Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XU Edinburgh, UK [3].
3
1] [2].
4
1] University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands [2].
5
1] International Agency for Research on Cancer (IARC), 69372 Lyon, France [2].
6
USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089-9175, USA.
7
University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands.
8
Statens Serum Institut, DK-2300 Copenhagen, Denmark.
9
Karolinska Institutet and Karolinska University Hospital, S-221 00 Stockholm, Sweden.
10
Cancer Prevention Institute of California, Fremont, California 94538, USA.
11
St Jude Children's Hospital, Cordova, Tennessee 38105, USA.
12
Centre Léon Bérard, UMR CNRS 5239-Université Lyon 1, 69008 Lyon, France.
13
University Medical Centre Freiburg, D-79085 Freiburg, Germany.
14
IDIBELL Institut Català d'Oncologia, 8907 Barcelona, Spain.
15
University of York, YO10 5DD York, UK.
16
German Cancer Research Centre, D-69120 Heidelberg, Germany.
17
CHU de Dijon, EA 4184, University of Burgundy, 21070 Dijon, France.
18
Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic.
19
City of Hope National Medical Center, Duarte, California 91010, USA.
20
Uppsala University, 75285 Uppsala, Sweden.
21
School of Nursing and Human Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland.
22
Icahn School of Medicine at Mount Sinai, New York City, New York 10029-6574, USA.
23
University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
24
Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, The Netherlands.
25
Mayo Clinic, Rochester, Minnesota 55905, USA.
26
MD Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA.
27
INSERM U557 (UMR Inserm; INRA; CNAM, Université Paris 13), 93017 Paris, France.
28
Norwegian University of Science and Technology, NO-7491 Trondheim, Norway.
29
MRC University of Glasgow Centre for Virus Research, Garscube Estate, University of Glasgow, G12 8QQ Glasgow, Scotland, UK.
30
Department of Human Genetics and Disease Diversity, Tokyo Medical and Dental University, Tokyo 104-0044, Japan.
31
International Agency for Research on Cancer (IARC), 69372 Lyon, France.
32
Clarient Pathology Services, Aliso Viejo, California 92656, USA.
33
Genome Quebec, Montreal, Canada H3A 0G1.
34
Institute of Occupational Health, University of Cagliari, Monserrato, 09042 Cagliari, Italy.
35
The University of Chicago, Chicago, Illinois 60637-5415, USA.
36
1] Karolinska Institutet and Karolinska University Hospital, S-221 00 Stockholm, Sweden [2] Harvard University School of Public Health, Boston, Massachusetts 02115, USA.
37
School of Cancer Sciences, University of Manchester, St Mary's Hospital, M13 0JH Manchester, UK.
38
1] The University of Chicago, Chicago, Illinois 60637-5415, USA [2].
39
1] MRC University of Glasgow Centre for Virus Research, Garscube Estate, University of Glasgow, G12 8QQ Glasgow, Scotland, UK [2].
40
1] Statens Serum Institut, DK-2300 Copenhagen, Denmark [2].

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, P(combined) = 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.

PMID:
24920014
PMCID:
PMC4055950
DOI:
10.1038/ncomms4856
[Indexed for MEDLINE]
Free PMC Article

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