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Nat Commun. 2015 Jan 8;6:5751. doi: 10.1038/ncomms6751.

A genome-wide association study of marginal zone lymphoma shows association to the HLA region.

Author information

1
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
2
Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland 20877, USA.
3
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
4
1] Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, Birmingham, Alabama 35233, USA [2] Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California 94720, USA.
5
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
6
1] Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d'Oncologia, IDIBELL, Barcelona 8907, Spain [2] Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona 8036, Spain.
7
1] Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen 2300, Denmark [2] Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
8
1] Department of Oncology and Pathology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm 17176, Sweden [2] Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala 75105, Sweden.
9
Department of Epidemiology &Biostatistics, University of California San Francisco, San Francisco, California 94118, USA.
10
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
11
Department of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, California 91030, USA.
12
1] Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z1L3 [2] Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada V5A1S6.
13
1] Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands [2] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.
14
1] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands [2] Institute for Risk Assessment Sciences, Utrecht University, Utrecht 3508 TD, The Netherlands.
15
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
16
Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA.
17
1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
18
Department of Epidemiology, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
19
Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen 2300, Denmark.
20
1] Department of Preventive Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA [2] Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
21
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
22
Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
23
1] Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z1L3 [2] School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada V6T1Z3.
24
1] Pathology, Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales 2109, Australia [2] Department of Histopathology, Douglass Hanly Moir Pathology, Macquarie Park, New South Wales 2113, Australia.
25
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut 06520, USA.
26
1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3053, Australia [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, Victoria 3010, Australia.
27
MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
28
1] Department of Population Health, New York University School of Medicine, New York, New York 10016, USA [2] Cancer Institute, New York University School of Medicine, New York, New York 10016, USA.
29
Department of Biomedical Science, University of Cagliari, Monserrato, Cagliari 09042, Italy.
30
1] Environmental Epidemiology of Cancer Group, Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Villejuif F-94807, France [2] UMRS 1018, Univ Paris Sud, Villejuif F-94807, France [3] Registre des hémopathies malignes de la Gironde, Institut Bergonié, Bordeaux 33076, France.
31
1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
32
Department of Health Sciences, University of York, York YO10 5DD, UK.
33
Health Studies Sector, Westat, Rockville, Maryland 20850, USA.
34
1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
35
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
36
1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA [2] College of Information Science and Technology, Dalian Maritime University, Dalian 116026, China.
37
Departments of Laboratory Medicine and Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
38
Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California 94720, USA.
39
Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio 43210, USA.
40
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98117, USA.
41
1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA [2] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.
42
Department of Medicine Solna, Karolinska Institutet, Stockholm 17176, Sweden.
43
1] Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98117, USA [2] Department of Environmental and Occupational Health, Drexel University School of Public Health, Philadelphia, Pennsylvania 19104, USA.
44
Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan 48201, USA.
45
The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
46
Group of Genetic Epidemiology, Section of Genetics, International Agency for Research on Cancer, Lyon 69372, France.
47
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU, Brno 65653, Czech Republic.
48
EA 4184, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon 21070, France.
49
Genetic Cancer Susceptibility Group, Section of Genetics, International Agency for Research on Cancer, Lyon 69372, France.
50
School of Nursing and Human Sciences, Dublin City University, Dublin 9, Ireland.
51
Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.
52
Sydney School of Public Health, The University of Sydney, Sydney, New South Wales 2006, Australia.
53
Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut 06520, USA.
54
1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3053, Australia [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, Victoria 3010, Australia [3] Human Genetics Foundation, Turin 10126, Italy.
55
1] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK [2] Human Genetics Foundation, Turin 10126, Italy.
56
Interdisciplinary Department of Medicine, University of Bari, Bari 70124, Italy.
57
Department of Pathological Anatomy, University of Bari, Bari 70124, Italy.
58
Environmental and Occupational Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Florence 50139, Italy.
59
1] Environmental Epidemiology of Cancer Group, Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Villejuif F-94807, France [2] UMRS 1018, Univ Paris Sud, Villejuif F-94807, France.
60
1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA [3] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
61
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki FI-00271, Finland.
62
Department of Health Studies, University of Chicago, Chicago, Illinois 60637, USA.
63
Center For Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg 79108, Germany.

Abstract

Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.

PMID:
25569183
PMCID:
PMC4287989
DOI:
10.1038/ncomms6751
[Indexed for MEDLINE]
Free PMC Article

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