CXCR5 polymorphisms in non-Hodgkin lymphoma risk and prognosis

Bridget Charbonneau, Alice H. Wang, Matthew J. Maurer, Yan Asmann, Clive S. Zent, Brian K. Link, Stephen Maxted Ansell, George J. Weiner, Nazan Ozsan, Andrew L Feldman, Thomas Elmer Witzig, Julie M Cunningham, Ahmet Dogan, Thomas Matthew Habermann, Susan L Slager, Anne J Novak, James R Cerhan

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1475-1484
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume62
Issue number9
DOIs
StatePublished - Sep 2013

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Follicular Lymphoma
Non-Hodgkin's Lymphoma
Peripheral T-Cell Lymphoma
Mantle-Cell Lymphoma
Lymphoma, Large B-Cell, Diffuse
B-Cell Chronic Lymphocytic Leukemia
CXCR5 Receptors
Single Nucleotide Polymorphism
Lymphoma
B-Lymphocytes
CCR Receptors
B-Lymphocyte Subsets
T-Lymphocytes
Disease Management
Dendritic Cells
Disease-Free Survival
Cell Movement
Alleles
Ligands
Skin

Keywords

  • Case-control
  • Non-Hodgkin lymphoma
  • Prognosis
  • Prospective cohort
  • SNPs

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

Cite this

CXCR5 polymorphisms in non-Hodgkin lymphoma risk and prognosis. / Charbonneau, Bridget; Wang, Alice H.; Maurer, Matthew J.; Asmann, Yan; Zent, Clive S.; Link, Brian K.; Ansell, Stephen Maxted; Weiner, George J.; Ozsan, Nazan; Feldman, Andrew L; Witzig, Thomas Elmer; Cunningham, Julie M; Dogan, Ahmet; Habermann, Thomas Matthew; Slager, Susan L; Novak, Anne J; Cerhan, James R.

In: Cancer Immunology, Immunotherapy, Vol. 62, No. 9, 09.2013, p. 1475-1484.

Research output: Contribution to journalArticle

Charbonneau, Bridget ; Wang, Alice H. ; Maurer, Matthew J. ; Asmann, Yan ; Zent, Clive S. ; Link, Brian K. ; Ansell, Stephen Maxted ; Weiner, George J. ; Ozsan, Nazan ; Feldman, Andrew L ; Witzig, Thomas Elmer ; Cunningham, Julie M ; Dogan, Ahmet ; Habermann, Thomas Matthew ; Slager, Susan L ; Novak, Anne J ; Cerhan, James R. / CXCR5 polymorphisms in non-Hodgkin lymphoma risk and prognosis. In: Cancer Immunology, Immunotherapy. 2013 ; Vol. 62, No. 9. pp. 1475-1484.
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AU - Asmann, Yan

AU - Zent, Clive S.

AU - Link, Brian K.

AU - Ansell, Stephen Maxted

AU - Weiner, George J.

AU - Ozsan, Nazan

AU - Feldman, Andrew L

AU - Witzig, Thomas Elmer

AU - Cunningham, Julie M

AU - Dogan, Ahmet

AU - Habermann, Thomas Matthew

AU - Slager, Susan L

AU - Novak, Anne J

AU - Cerhan, James R

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