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Abstract Number: 2840

Are There Genetic Predispositions to Diffuse Large B-Cell Lymphoma (DLBCL) in Systemic Lupus (SLE)?

Sasha Bernatsky1, Ann E. Clarke2, Rosalind Ramsey-Goldman3, Patrick Gaffney4, John Spinelli5, Sophia Wang6 and Timothy J. Vyse7, 1Divisions of Rheumatology and Clinical Epidemiology, McGill University Health Centre, Montreal, QC, Canada, 2Division of Rheumatology, University of Calgary, Calgary, AB, Canada, 3FSM, Northwestern University, Chicago, IL, 4Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 5School of Population and Public Health, University of British Columbia, Vancouver, QC, Canada, 6Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, Duarte, CA, 7Department of Medical and Molecular Genetics, King's College London, London, United Kingdom

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: cancer and malignancy, SLE

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Session Information

Date: Tuesday, November 15, 2016

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment - Poster III: Biomarkers and Nephritis

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Are there genetic predispositions to diffuse large B-cell lymphoma (DLBCL) in systemic lupus (SLE)?   Sasha Bernatsky1, Ann E. Clarke2, Rosalind Ramsey-Goldman3, Patrick M. Gaffney4, John Spinelli5, Sophia Wang6, Timothy Vyse7   1Division of Rheumatology, Department of Medicine, McGill University, Montreal, QC H3G 1A4, Canada; 2Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada; 3Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA 4Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. 5University of British Columbia, Vancouver, British Columbia. 6Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA, USA 7Department of Medical & Molecular Genetics, King’s College London, Guy’s Hospital, London SE1 9RT, UK;      

Background/Purpose: The determinants of the increased risk of non-Hodgkin Lymphoma (NHL) in systemic lupus (SLE) are unclear. The most common type of NHL in SLE (as in the general population) is the Diffuse Large B-Cell lymphoma (DLBCL) subtype. Our purpose was to identify if known susceptibility loci for DLBCL occur more frequently in SLE.

Methods: We used data from a recent GWAS of SLE conducted in a North American case-control sample of European ancestry Our study comprised 7,219 SLE cases and 15,991 non-SLE controls, genotyped on Affymetrix Genome-Wide Human SNP Array 6.0. We studied 4 loci that have been associated with DLBCL in recent GWAS studies, to determine if these DLBCL-associated SNPs occur more frequently in SLE versus the general population.  

Results:  For the DLBCL SNP of interest rs2621416 on 6p21.32 (associated with HLA-DOB 1), while the G (versus A) risk allele is a risk factor for DLBCL, the same allele is protective for SLE (odds ratio, OR for the G allele in SLE versus the general population was 0.78, 95% confidence interval, CI 0.63, 0.97, p value 0.023).  For the DLBCL SNP of interest rs4530903 on 6p21.32 (associated with HLA-DQA1), while the T (versus C) risk allele is a risk factor for DLBCL, the A allele was possibly protective for SLE (OR for the A allele in SLE versus the general population was 0.72, 95% CI 0.50, 1.02, p value 0.066). For the other two DLBCL SNPs of interest, the SLE OR was close to 1 with a wide confidence interval.

Conclusion: We did not identify an increased occurrence of known susceptibility loci for DLBCL in SLE in these analyses.   Odds Ratio Estimates for SLE risk, for Diffuse Large B Cell Lymphoma (DLBCL)-related SNPs

DLBCL-related SNP A1 SLE OR

95 % CI

P value Chromosome MAF_ALL MAF_Case MAF_Control Nearest Gene
rs2621416 G

0.78

(0.63, 0.97)

0.023

p21.32

0.25

0.23

0.28

HLA-DOB

rs4530903 A

0.72

(0.50, 1.02)

0.066

p21.32

0.08

0.07

0.10

HLA-DQA1

rs948562 G

1.13

(0.87, 1.45)

0.367

q12.1

0.17

0.17

0.17

ZFP91-CNTF

rs4733601 A

1.04

(0.85, 1.27)

0.719

q24.21

0.50

0.51

0.48

MIR1208

 


Disclosure: S. Bernatsky, None; A. E. Clarke, None; R. Ramsey-Goldman, None; P. Gaffney, None; J. Spinelli, None; S. Wang, None; T. J. Vyse, None.

To cite this abstract in AMA style:

Bernatsky S, Clarke AE, Ramsey-Goldman R, Gaffney P, Spinelli J, Wang S, Vyse TJ. Are There Genetic Predispositions to Diffuse Large B-Cell Lymphoma (DLBCL) in Systemic Lupus (SLE)? [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/are-there-genetic-predispositions-to-diffuse-large-b-cell-lymphoma-dlbcl-in-systemic-lupus-sle/. Accessed .
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