Journal
BLOOD
Volume 119, Issue 2, Pages 469-475Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-03-343921
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Funding
- National Institutes of Health [CA110836, HD0433871, CA129045, CA40046, CA55727, CA58839]
- United States Army Medical Research and Materiel Command (Department of Defense) [PR054600]
- American Cancer Society Illinois Division
- American Lebanese Syrian Associated Charities
- Leukemia & Lymphoma Society [TR6137-07]
- Cancer Research Foundation
- National Cancer Institute
- National Institutes of Health, Department of Health and Human Services [N01-PC-35139, N01-PC-35136]
- National Cancer Institute [263-MQ-417755]
- California Department of Health Services [103885]
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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 x 10(-10)), rs204999 (P = 1.44 x 10(-9)), and rs2858870 (P = 1.69 x 10(-8)). We also confirmed a previously reported association in the same region, rs6903608 (P = 3.52 x 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 x 10(-6); GAATC, OR = 0.4, P = 1.16 x 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. (Blood. 2012;119(2):469-475)
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