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A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32
Journal article   Open access   Peer reviewed

A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32

Wendy Cozen, Dalin Li, Timothy Best, David J Van Den Berg, Pierre-Antoine Gourraud, Victoria K Cortessis, Andrew D Skol, Thomas M Mack, Sally L Glaser, Lawrence M Weiss, …
Blood, Vol.119(2), pp.469-475
01/12/2012
DOI: 10.1182/blood-2011-03-343921
PMCID: PMC3257012
PMID: 22086417
url
https://doi.org/10.1182/blood-2011-03-343921View
Published (Version of record) Open Access

Abstract

Nodular sclerosing Hodgkin lymphoma (NSHL) is a distinct, highly heritable Hodgkin lymphoma subtype. We undertook a genome-wide meta-analysis of 393 European-origin adolescent/young adult NSHL patients and 3315 controls using the Illumina Human610-Quad Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We identified 3 single nucleotide polymorphisms (SNPs) on chromosome 6p21.32 that were significantly associated with NSHL risk: rs9268542 ( P = 5.35 × 10 −10 ), rs204999 ( P = 1.44 × 10 −9 ), and rs2858870 ( P = 1.69 × 10 −8 ). We also confirmed a previously reported association in the same region, rs6903608 ( P = 3.52 × 10 −10 ). rs204999 and rs2858870 were weakly correlated (r 2 = 0.257), and the remaining pairs of SNPs were not correlated (r 2 < 0.1). In an independent set of 113 NSHL cases and 214 controls, 2 SNPs were significantly associated with NSHL and a third showed a comparable odds ratio (OR). These SNPs are found on 2 haplotypes associated with NSHL risk (rs204999-rs9268528-rs9268542-rs6903608-rs2858870; AGGCT, OR = 1.7, P = 1.71 × 10 −6 ; GAATC, OR = 0.4, P = 1.16 × 10 −4 ). All individuals with the GAATC haplotype also carried the HLA class II DRB1*0701 allele. In a separate analysis, the DRB1*0701 allele was associated with a decreased risk of NSHL (OR = 0.5, 95% confidence interval = 0.4, 0.7). These data support the importance of the HLA class II region in NSHL etiology.
Lymphoid Neoplasia Clinical Trials and Observations

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