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The Human Leukocyte Antigen Class I Region Is Associated with EBV-Positive Hodgkin's Lymphoma: HLA-A and HLA Complex Group 9 Are Putative Candidate Genes

Departments of ¹ Medical Genetics, ² Pathology, and ³ Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; ⁴ LRF Virus Centre, Institute of Comparative Medicine, University of Glasgow, Glasgow, United Kingdom; and ⁵ Cancer Immunogenetics Laboratory, University of Manchester, Manchester, United Kingdom

Requests for reprints: Gerald J. te Meerman, A. Deusinglaan 4, 9713 AW Groningen, the Netherlands. Phone: 31-50-363-2939; Fax: 31-50-363-3113. E-mail: G.J.te.Meerman{at}med.UMCG.nl

Various studies have indicated that the human leukocyte antigen (HLA) region is associated with Hodgkin's lymphoma. We recently showed a specific association of the HLA class I region with EBV-positive Hodgkin's lymphoma cases. One haplotype of two consecutive microsatellite markers (D6S265 and D6S510) was overrepresented in the patient group, whereas another haplotype was underrepresented. Here, we did fine mapping of this region of 400 kb as a next step to find the causative single-nucleotide polymorphism(s) (SNP). To select candidate SNPs for screening the total study population, several known SNPs were determined by sequencing two individuals homozygous for either of the above-mentioned associated haplotypes. Seven SNPs displayed different alleles in these two individuals and were therefore analyzed in the total study population, including 238 Hodgkin's lymphoma patients and 365 family-based controls. All seven SNPs showed significant association with the EBV-positive patient group. Two of these SNPs were analyzed in a Scottish Hodgkin's lymphoma population and revealed significant associations as well. The associated SNPs are located nearby two putative candidate genes: HLA-A and HLA complex group 9. HLA-A represents the most interesting target because of its consistent expression in EBV-positive Hodgkin's lymphoma cases and its ability to present EBV-derived peptides to cytotoxic T cells. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2280–4)

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