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 Vyse^{7   1}Division 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