title: Refining the prostate cancer genetic association within the JAZF1 gene on chromosome 7p15.2.
abstract: BACKGROUND
  Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P=2.14x10(-6)), with a suggestion of stronger association with aggressive disease (P=1.2x10(-7)).
  
  
  METHODS
  In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry.
  
  
  RESULTS
  The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P=7.79x10(-11); ORHET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P=1.60x10(-4) for aggressive cancer, n=4,597; P=3.25x10(-8) for nonaggressive cancer, n=4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P=0.587), body stature (rs849141, tagged by rs849136; P=0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P=0.657).
  
  
  CONCLUSIONS
  rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry.
  
  
  CONCLUSIONS
  Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa.
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 8717 Grovemont Circle, Bethesda, MD 20892-4605, USA. prokuninal@mail.nih.gov
authors.forename: Ludmila
authors.initials: L
authors.lastname: Prokunina-Olsson
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Fu
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Jacobs
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Heather
authors.initials: H
authors.lastname: Spencer Feigelson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
authors.forename: W Ryan
authors.initials: WR
authors.lastname: Diver
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Stephanie
authors.initials: S
authors.lastname: Weinstein
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cancel-Tassin
authors.forename: Olivier
authors.initials: O
authors.lastname: Cussenot
authors.forename: Antoine
authors.initials: A
authors.lastname: Valeri
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Andriole
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Laurence
authors.initials: L
authors.lastname: Kolonel
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Afshan
authors.initials: A
authors.lastname: Siddiq
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Ruth
authors.initials: R
authors.lastname: Travis
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Isaacs
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Lars J
authors.initials: LJ
authors.lastname: Vatten
authors.forename: Kristian
authors.initials: K
authors.lastname: Hveem
authors.forename: Merethe
authors.initials: M
authors.lastname: Kumle
authors.forename: Margaret
authors.initials: M
authors.lastname: Tucker
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Fraumeni
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
mesh_terms: D016022:Case-Control Studies; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C430460:JAZF1 protein, human; D009363:Neoplasm Proteins
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