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Lupus Sci Med. 2017 Nov 12;4(1):e000187. doi: 10.1136/lupus-2016-000187. eCollection 2017.

Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma.

Author information

1
Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Canada.
2
BC Cancer Research Centre and School of Population and Public Health, University of British Columbia, Vancouver, Canada.
3
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
4
Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, and Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
5
Feinberg School of Medicine, Northwestern University, Chicago, USA.
6
Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, Duarte, USA.
7
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
8
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
9
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA.
10
Hematology Unit, Ospedale Oncologico di Riferimento Regionale 'A. Businco', Cagliari, Italy.
11
Department of Medicine, Mayo Clinic, Rochester, USA.
12
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Jacksonville, USA.
13
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
14
Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
15
Slone Epidemiology Center, Boston University, Boston, USA.
16
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
17
Department of Epidemiology, German Institute for Human Nutrition, Potsdam, Germany.
18
The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
19
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA.
20
International Agency for Research on Cancer (IARC), Lyon, France.
21
Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada.
22
Department of Health Sciences Research, Mayo Clinic, Rochester, USA.
23
Epidemiology of childhood and adolescent cancers Group, Inserm, Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France.
24
Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, USA.
25
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, USA.
26
INSERM U1052, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon, France.
27
Department of Preventive Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, USA.
28
Department of Health Sciences, University of York, York, UK.
29
Department of Environmental and Occupational Health, Dornsife School of Public Health at Drexel University, Philadelphia, USA.
30
CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
31
Department of Surgery and Translational Medicine, Section of Anatomo-Pathology, University of Florence, Florence, Italy.
32
Epidemiology Research Program, American Cancer Society, Atlanta, USA.
33
Departments of Laboratory Medicine and Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.
34
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic.
35
Department of Hematology, Centre Léon Bérard, Lyon, France.
36
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
37
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
38
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
39
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, USA.
40
Lymphoid Malignancies Unit, Henri Mondor Hospital and University Paris Est, Créteil, France.
41
Division ofHealth Surveillance and Research, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
42
Department of Biostatistics, Yale School of Public Health, New Haven, USA.
43
Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, USA.
44
Icahn Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
45
Sydney School of Public Health, The University of Sydney, Sydney, Australia.
46
Westat Inc, Rockville, USA.
47
Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, USA.
48
Registre des Hémopathies Malignes de Côte d'Or, EA 4184, Univ. Bourgogne Franche-Comté and Dijon University Hospital, Dijon, France.
49
Department of Pathology, AP-HP, Necker Enfants malades, Université Paris Descartes, Sorbonne Paris Cité, France.
50
Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany.
51
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, USA.
52
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
53
Ontario Health Study, Toronto, Canada.
54
Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Italy.
55
Department of Hematology, Hospices Civils de Lyon, Pierre benite Cedex, France.
56
Human Genetics Foundation, Turin, Italy.
57
Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, USA.
58
Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, USA.
59
Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Australia.
60
School of Nursing and Human Sciences, Dublin City University, Dublin, Ireland.
61
Centre Heni Becquerel, Université de Rouen, Rouen, France.
62
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA.
63
Danish Cancer Society Research Center, Copenhagen, Denmark.
64
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
65
Centre for Big Data Research in Health, University of New South Wales, Sydney, Australia.
66
Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
67
MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
68
Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
69
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
70
Department of Population Health, New York University School of Medicine, New York, USA.
71
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, USA.
72
Department of Epidemiology, Brown School of Public Health, Providence, USA.
73
Department of Biomedical Science, University of Cagliari, Monserrato, Italy.
74
Division of Rheumatology, University of Calgary, Calgary, Canada.

Abstract

Objective:

Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL.

Methods:

GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis.

Results:

Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765.

Conclusions:

These data suggest several plausible genetic links between DLBCL and SLE.

KEYWORDS:

Systemic lupus; lymphoma; malignancy

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