Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways
Kleinstern, G.; Yan, H.; Hildebrandt, M.A.T.; Vijai, J.; Berndt, S.I.; Ghesquières, H.; McKay, J.; Nieters, A.; Ye, Y.; Monnereau, A.; Brooks-Wilson, A.R.; Lan, Q.; Melbye, M.; Jackson, R.D.; Teras, L.R.; Purdue, M.P.; Vajdic, C.M.; Vermeulen, R.C.H.; Giles, G.G.; Cocco, P.L.; Birmann, B.M.; Kraft, P.; Albanes, D.; Zeleniuch-Jacquotte, A.; Crouch, S.; Sarangi, V.; Asmann, Y.; Offit, K.; Salles, G.; Smedby, K.E.; Skibola, C.F.; Slager, S.L.; Rothman, N.; Chanock, S.J.; Cerhan, J.R.
(2020) Human Molecular Genetics, volume 29, issue 1, pp. 70 - 79
(Article)
Abstract
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
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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.
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ISSN: 0964-6906
Publisher: Oxford University Press
Note: Cited By :7 Export Date: 8 December 2021
(Peer reviewed)