Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways.
- Mayo Clinic, Rochester, MN, USA.
- University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
- National Cancer Institute, Bethesda, MD, USA.
- Centre Léon Bérard, Lyon, France.
- International Agency for Research on Cancer, Lyon, France.
- City of Hope Beckman Research Institute, Duarte, CA, USA.
- Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Freiburg, Germany.
- Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France.
- BC Cancer Agency, Vancouver, BC, Canada.
- Statens Serum Institut, Copenhagen, Denmark.
- The Ohio State University, Columbus, OH, USA.
- American Cancer Society, Atlanta, GA, USA.
- University of New South Wales, Sydney, Australia.
- University Medical Center Utrecht, Utrecht, The Netherlands.
- Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Australia.
- Department of Medical Sciences and Public Health, Occupational Health Section, University of Cagliari, Monserrato, Italy.
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- NYU School of Medicine, New York, NY, USA.
- University of York, York, United Kingdom.
- Yale School of Public Health, New Haven, CT, USA.
- Mayo Clinic, Jacksonville, FL, USA.
- Hospices Civils de Lyon, Lyon, France.
- Karolinska Institutet, Stockholm, Sweden.
- Emory University, Atlanta, GA, USA.
We previously identified five single nucleotide polymorphisms (SNPs) at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate two loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5662 cases and 9237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF] = 0.40) was associated with DLBCL risk [odds ratio (OR) = 0.83, P = 3.62 × 10-13]. rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5510 cases and 12 817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF = 0.45) was also associated with DLBCL risk (OR = 1.20, P = 2.31 × 10-12). This SNP is 29 426-bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.
- 2010-0008: A genome-wide association study of non-Hodgkin lymphoma (Sonja Berndt - 2010)