Abstract
Abstract 5071: A genome-wide association study suggests evidence of variants at 6p21.32 associated with marginal zone lymphoma
Cancer research (Chicago, Ill.), Vol.74(19_Supplement), pp.5071-5071
10/01/2014
DOI: 10.1158/1538-7445.AM2014-5071
Abstract
Abstract
Marginal zone lymphomas (MZL) are a group of indolent non-Hodgkin's B-cell lymphomas (NHL) comprising extranodal MZL of mucosa-associated lymphoid tissue (MALT) type, splenic MZL and nodal MZL. MZL comprises 7-12% of adult NHLs. The genetic etiology of MZL is poorly understood. To better understand the genetic risk factors for MZL, we conducted the first genome-wide association study (GWAS) of this lymphoid malignancy. The GWAS included 824 MZL cases and 6,220 controls of European ancestry from 22 studies of NHL. Genotyping was carried out at the Cancer Genomics Research Laboratory (CGR) of NCI using Illumina Human OmniExpress arrays. Standard genotyping quality controls were performed. Imputation of common SNPs was performed using IMPUTE2 software and 1000 Genomes Project release version 3 data. Association testing was subsequently performed using SNPTEST, assuming a log-additive genetic model adjusting for age, gender and three significant eigenvectors. We identified one locus at 6p21.32 within the HLA class II region that attained genome-wide significance (P<5x10-8). When a small number of additional cases (n=58) and controls (n=66) genotyped using Taqman assays were included, rs9461741 (BTNL2) was associated with an increased risk of MZL (per-allele odds ratio = 2.38, 95% confidence interval: 1.74-3.24; P=4.32x10-8). Other SNPs at the 6p21.32 locus were also highly associated with MZL, suggesting that this is unlikely to be a chance finding. Promising signals yet to be confirmed were also observed on chromosomes 3 and 14. The BTNL2 protein has extracellular immunoglobulin domains and is expressed in multiple tissues including various immune organs and the gut and it inhibits T-cell activation. Genetic variability at BTNL2 has been associated with inflammatory and infectious phenotypes, highlighting the importance of this locus for immune diseases. In conclusion, findings from this GWAS identify the HLA class II region as an important susceptibility locus for MZL.
Citation Format: Joseph Vijai, Zhaoming Wang, Sonja I. Berndt, Susan L. Slager, James R. Cerhan, Christine Skibola, Sophia S. Wang, Angela R. Brooks-Wilson, Silvia de Sanjose, Paige M. Bracci, Mads Melbye, Bengt Glimelius, Rebecca D. Jackson, Wendy Cozen, Nikolaus Becker, Lauren R. Teras, John J. Spinelli, Jenny Turner, Qing Lan, Mark P. Purdue, Kimberly A. Bertrand, Kenneth Offit, Paolo Vineis, Brian K. Link, Graham G. Giles, Anne Zelenuich-Jacquotte, Alain Monnereau, Maria Grazia Ennas, Demetrius Albanes, Laurie Burdett, Nathaniel Rothman, Stephen J. Chanock, Alexandra Nieters, On behalf of the NHL GWAS Consortium. A genome-wide association study suggests evidence of variants at 6p21.32 associated with marginal zone lymphoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5071. doi:10.1158/1538-7445.AM2014-5071
Details
- Title: Subtitle
- Abstract 5071: A genome-wide association study suggests evidence of variants at 6p21.32 associated with marginal zone lymphoma
- Creators
- Joseph VijaiZhaoming WangSonja I. BerndtSusan L. SlagerJames R. CerhanChristine SkibolaSophia S. WangAngela R. Brooks-WilsonSilvia de SanjoséPaige M. BracciMads MelbyeBengt GlimeliusRebecca D. JacksonWendy CozenNikolaus BeckerLauren R. TerasJohn J. SpinelliJenny TurnerQing LanMark P. PurdueKimberly A. BertrandKenneth OffitPaolo VineisBrian K. LinkGraham G. GilesAnne Zelenuich-JacquotteAlain MonnereauMaria Grazia EnnasDemetrius AlbanesLaurie BurdettNathaniel RothmanStephen J. ChanockAlexandra Nieters
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.74(19_Supplement), pp.5071-5071
- DOI
- 10.1158/1538-7445.AM2014-5071
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 10/01/2014
- Academic Unit
- Epidemiology; Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984362683302771
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