Genetic variation in B-cell-activating factor is associated with an increased risk of developing B-cell non-Hodgkin lymphoma

Anne J Novak, Susan L Slager, Zachary S. Fredericksen, Alice H. Wang, Michelle M. Manske, Steven Ziesmer, Mark Liebow, William R. Macon, Stacey R. Dillon, Thomas Elmer Witzig, James R Cerhan, Stephen Maxted Ansell

Research output: Contribution to journalArticle

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Abstract

Elevated B-cell-activating factor (BAFF; TNFSF13B) levels have been found in patients with B-cell malignancies and autoimmune diseases, suggesting that it may play a pathogenic role. We previously found that a single nucleotide polymorphism (SNP) in the TNFSF13B promoter resulted in increased transcription, suggesting that genetic variation in TNFSF13B may influence its expression. We therefore wanted to determine if genetic variation in TNFSF13B is associated with high BAFF levels and non-Hogkin lymphoma (NHL) risk. We genotyped 9 tagSNPs within TNFSF13B in a clinic-based study of 441 NHL cases and 475 matched controls and evaluated the association of individual SNPs with risk of NHL; 3 tagSNPs were significant (P < 0.05). When categorized into low-, moderate-, and high-risk groups based on risk alleles, we found the permutation-corrected odds ratio for the trend to be 1.43 (P = 0.0019) for risk of B-cell NHL, 1.69 (P = 0.0093) for diffuse large B-cell lymphoma, 1.43 (P = 0.029) for follicular lymphoma, and 1.06 (P = 0.21) for chronic lymphocytic leukemia/small lymphocytic lymphoma. The mean serum BAFF level in those who carried the low-risk alleles was 2 ng/mL compared with 4.3 ng/mL in those with the high-risk alleles (P = 0.02). Taken together, our data suggest that genetic variation in the TNFSF13B gene is significantly associated with NHL risk and elevated serum BAFF levels.

Original languageEnglish (US)
Pages (from-to)4217-4224
Number of pages8
JournalCancer Research
Volume69
Issue number10
DOIs
StatePublished - May 15 2009

Fingerprint

B-Cell Activating Factor
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
Lymphoma
Alleles
B-Cell Chronic Lymphocytic Leukemia
Single Nucleotide Polymorphism
B-Lymphocytes
Follicular Lymphoma
Lymphoma, Large B-Cell, Diffuse
Serum
Autoimmune Diseases
Odds Ratio

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Genetic variation in B-cell-activating factor is associated with an increased risk of developing B-cell non-Hodgkin lymphoma. / Novak, Anne J; Slager, Susan L; Fredericksen, Zachary S.; Wang, Alice H.; Manske, Michelle M.; Ziesmer, Steven; Liebow, Mark; Macon, William R.; Dillon, Stacey R.; Witzig, Thomas Elmer; Cerhan, James R; Ansell, Stephen Maxted.

In: Cancer Research, Vol. 69, No. 10, 15.05.2009, p. 4217-4224.

Research output: Contribution to journalArticle

Novak, Anne J ; Slager, Susan L ; Fredericksen, Zachary S. ; Wang, Alice H. ; Manske, Michelle M. ; Ziesmer, Steven ; Liebow, Mark ; Macon, William R. ; Dillon, Stacey R. ; Witzig, Thomas Elmer ; Cerhan, James R ; Ansell, Stephen Maxted. / Genetic variation in B-cell-activating factor is associated with an increased risk of developing B-cell non-Hodgkin lymphoma. In: Cancer Research. 2009 ; Vol. 69, No. 10. pp. 4217-4224.
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abstract = "Elevated B-cell-activating factor (BAFF; TNFSF13B) levels have been found in patients with B-cell malignancies and autoimmune diseases, suggesting that it may play a pathogenic role. We previously found that a single nucleotide polymorphism (SNP) in the TNFSF13B promoter resulted in increased transcription, suggesting that genetic variation in TNFSF13B may influence its expression. We therefore wanted to determine if genetic variation in TNFSF13B is associated with high BAFF levels and non-Hogkin lymphoma (NHL) risk. We genotyped 9 tagSNPs within TNFSF13B in a clinic-based study of 441 NHL cases and 475 matched controls and evaluated the association of individual SNPs with risk of NHL; 3 tagSNPs were significant (P < 0.05). When categorized into low-, moderate-, and high-risk groups based on risk alleles, we found the permutation-corrected odds ratio for the trend to be 1.43 (P = 0.0019) for risk of B-cell NHL, 1.69 (P = 0.0093) for diffuse large B-cell lymphoma, 1.43 (P = 0.029) for follicular lymphoma, and 1.06 (P = 0.21) for chronic lymphocytic leukemia/small lymphocytic lymphoma. The mean serum BAFF level in those who carried the low-risk alleles was 2 ng/mL compared with 4.3 ng/mL in those with the high-risk alleles (P = 0.02). Taken together, our data suggest that genetic variation in the TNFSF13B gene is significantly associated with NHL risk and elevated serum BAFF levels.",
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AU - Wang, Alice H.

AU - Manske, Michelle M.

AU - Ziesmer, Steven

AU - Liebow, Mark

AU - Macon, William R.

AU - Dillon, Stacey R.

AU - Witzig, Thomas Elmer

AU - Cerhan, James R

AU - Ansell, Stephen Maxted

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AB - Elevated B-cell-activating factor (BAFF; TNFSF13B) levels have been found in patients with B-cell malignancies and autoimmune diseases, suggesting that it may play a pathogenic role. We previously found that a single nucleotide polymorphism (SNP) in the TNFSF13B promoter resulted in increased transcription, suggesting that genetic variation in TNFSF13B may influence its expression. We therefore wanted to determine if genetic variation in TNFSF13B is associated with high BAFF levels and non-Hogkin lymphoma (NHL) risk. We genotyped 9 tagSNPs within TNFSF13B in a clinic-based study of 441 NHL cases and 475 matched controls and evaluated the association of individual SNPs with risk of NHL; 3 tagSNPs were significant (P < 0.05). When categorized into low-, moderate-, and high-risk groups based on risk alleles, we found the permutation-corrected odds ratio for the trend to be 1.43 (P = 0.0019) for risk of B-cell NHL, 1.69 (P = 0.0093) for diffuse large B-cell lymphoma, 1.43 (P = 0.029) for follicular lymphoma, and 1.06 (P = 0.21) for chronic lymphocytic leukemia/small lymphocytic lymphoma. The mean serum BAFF level in those who carried the low-risk alleles was 2 ng/mL compared with 4.3 ng/mL in those with the high-risk alleles (P = 0.02). Taken together, our data suggest that genetic variation in the TNFSF13B gene is significantly associated with NHL risk and elevated serum BAFF levels.

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