title: Mapping of the IRF8 gene identifies a 3'UTR variant associated with risk of chronic lymphocytic leukemia but not other common non-Hodgkin lymphoma subtypes.
abstract: BACKGROUND
  Our genome-wide association study (GWAS) of chronic lymphocytic leukemia (CLL) identified 4 highly correlated intronic variants within the IRF8 gene that were associated with CLL. These results were further supported by a recent meta-analysis of our GWAS with two other GWAS of CLL, supporting the IRF8 gene as a strong candidate for CLL risk.
  
  
  METHODS
  To refine the genetic association of CLL risk, we conducted Sanger sequencing of IRF8 in 94 CLL cases and 96 controls. We then conducted fine mapping by genotyping 39 variants (of which 10 were identified from sequencing) in 745 CLL cases and 1,521 controls. We also assessed these associations with risk of other non-Hodgkin lymphoma (NHL) subtypes.
  
  
  RESULTS
  The strongest association with CLL risk was observed with a common single-nucleotide polymorphism (SNP) located within the 3' untranslated region (UTR) of IRF8 (rs1044873, log additive OR = 0.7, P = 1.81 × 10(-6)). This SNP was not associated with the other NHL subtypes (all P > 0.05).
  
  
  CONCLUSIONS
  We provide evidence that rs1044873 in the IRF8 gene accounts for the initial GWAS signal for CLL risk. This association appears to be unique to CLL with little support for association with other common NHL subtypes. Future work is needed to assess functional role of IRF8 in CLL etiology.
  
  
  CONCLUSIONS
  These data provide support that a functional variant within the 3'UTR of IRF8 may be driving the GWAS signal seen on 16q24.1 for CLL risk.
authors: Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. slager@mayo.edu
authors: Susan L
authors: SL
authors: Slager
authors: Sara J
authors: SJ
authors: Achenbach
authors: Yan W
authors: YW
authors: Asmann
authors: Nicola J
authors: NJ
authors: Camp
authors: Kari G
authors: KG
authors: Rabe
authors: Lynn R
authors: LR
authors: Goldin
authors: Timothy G
authors: TG
authors: Call
authors: Tait D
authors: TD
authors: Shanafelt
authors: Neil E
authors: NE
authors: Kay
authors: Julie M
authors: JM
authors: Cunningham
authors: Alice H
authors: AH
authors: Wang
authors: J Brice
authors: JB
authors: Weinberg
authors: Aaron D
authors: AD
authors: Norman
authors: Brian K
authors: BK
authors: Link
authors: Jose F
authors: JF
authors: Leis
authors: Celine M
authors: CM
authors: Vachon
authors: Mark C
authors: MC
authors: Lanasa
authors: Neil E
authors: NE
authors: Caporaso
authors: Anne J
authors: AJ
authors: Novak
authors: James R
authors: JR
authors: Cerhan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology*; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult; D000099185:Interferon Regulatory Factor-8
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; D050835:Interferon Regulatory Factors; D000099185:Interferon Regulatory Factor-8