Abstract 4717: A search for overlapping HLA risk loci between NHL and autoimmune diseases

Abstract

Abstract Non-Hodgkin lymphoma (NHL) is a group of B- and T-cell neoplasms originating primarily from the lymph nodes, and represents the most common hematological malignancy in the United States. We recently conducted a genome-wide association study (GWAS) using DNA pools and identified a new risk locus for follicular lymphoma (FL) in the Class 1 human leukocyte antigen (HLA) region on chromosome 6. Currently, we are following up these results in a second GWAS using a subset of 757 NHL cases and 811 controls from a larger case-control study of NHL based in the San Francisco Bay Area using the Illumina HumanCNV370-Duo BeadChip. In the preliminary scan, we found additional evidence of Class 1 HLA loci that influence FL susceptibility, as well as loci in the Class 2 region, suggesting the importance of HLA genetic variation in FL risk. There is also clear evidence that HLA Class 1 and Class 2 loci confer genetic susceptibility to autoimmune diseases such as Crohn's disease (CD), type 1 diabetes (T1D), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Thus, because a history of autoimmune disease may increase risk of NHL, we explored whether HLA-region risk loci are common between these autoimmune diseases and NHL. Using genetic data available from the Wellcome Trust Case-Control Consortium (WTCCC) for CD and the software package BEAGLE 3.0.3, we imputed SNPs to look for association signals in the HLA region. SNPs were imputed based on CD genotyped SNPs and haplotype information from unrelated CEU samples in the HapMap phase II data. A Cochran-Armitage test for an additive genetic effect implemented in PLINK v1.05 was subsequently performed to test the genotype-phenotype associations of genotyped and imputed SNPs. Our preliminary results suggest associations in the HLA Class 2 region near the HLA-DQA2 and HLA-DQB2 genes, providing evidence that overlapping risk loci may exist between FL and CD. We are currently expanding our analysis to include genetic data for other autoimmune diseases available from WTCCC such as T1D and RA. These analyses will contribute new data about genetic variation in plausible HLA region pathways and will help to identify potentially functional genetic factors that contribute to lymphoma susceptibility. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4717.