title: Genetic variation in B-cell-activating factor is associated with an increased risk of developing B-cell non-Hodgkin lymphoma.
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.
authors.affiliation: Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Novak
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Fredericksen
authors.forename: Alice H
authors.initials: AH
authors.lastname: Wang
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Manske
authors.forename: Steven
authors.initials: S
authors.lastname: Ziesmer
authors.forename: Mark
authors.initials: M
authors.lastname: Liebow
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.forename: Stacey R
authors.initials: SR
authors.lastname: Dillon
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D053264:B-Cell Activating Factor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007484:Iowa; D016393:Lymphoma, B-Cell / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014922:Wisconsin; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor; C505719:TNFSF13B protein, human