CXCR5 polymorphisms in non-Hodgkin lymphoma risk and prognosis |
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Authors: | Bridget Charbonneau Alice H Wang Matthew J Maurer Yan W Asmann Clive S Zent Brian K Link Stephen M Ansell George J Weiner Nazan Ozsan Andrew L Feldman Thomas E Witzig Julie M Cunningham Ahmet Dogan Thomas M Habermann Susan L Slager Anne J Novak James R Cerhan |
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Institution: | 1. Department of Health Sciences Research, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA 2. Division of Hematology, Department of Internal Medicine, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA 3. Division of Hematology, Oncology, Blood and Marrow Transplantation, Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, IA, USA 4. Department of Pathology, Faculty of Medicine, Ege University, Bornova, ?zmir, Turkey 5. Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA
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Abstract: | CXCR5 chemokine (C-X-C motif) receptor 5; also known as Burkitt lymphoma receptor 1 (BCR1)] is expressed on mature B-cells, subsets of CD4+ and CD8+ T-cells, and skin-derived migratory dendritic cells. Together with its ligand, CXCL13, CXCR5 is involved in guiding B-cells into the B-cell zones of secondary lymphoid organs as well as T-cell migration. This study evaluated the role of common germline genetic variation in CXCR5 in the risk and prognosis of non-Hodgkin lymphoma (NHL) using a clinic-based study of 1,521 controls and 2,694 NHL cases including 710 chronic lymphocytic leukemia/small lymphocytic lymphoma, 586 diffuse large B-cell lymphoma (DLBCL), 588 follicular lymphoma (FL), 137 mantle cell lymphoma (MCL), 230 marginal zone lymphoma (MZL), and 158 peripheral T-cell lymphoma (PTCL). Of the ten CXCR5 tag SNPs in our study, five were associated with risk of NHL, with rs1790192 having the strongest association (OR 1.19, 95 % CI 1.08–1.30; p = 0.0003). This SNP was most strongly associated with the risk of FL (OR 1.44, 95 % CI 1.25–1.66; p = 3.1 × 10?7), with a lower degree of association with DLBCL (OR 1.16, 95 % CI 1.01–1.33; p = 0.04) and PTCL (OR 1.29, 95 % CI 1.02–1.64; p = 0.04) but no association with the risk of MCL or MZL. For FL patients that were observed as initial disease management, the number of minor alleles of rs1790192 was associated with better event-free survival (HR 0.64; 95 % CI 0.47–0.87; p = 0.004). These results provide additional evidence for a role of host genetic variation in CXCR5 in lymphomagenesis, particularly for FL. |
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