title: Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP.
abstract: BACKGROUND
  The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment.
  
  
  METHODS
  We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study.
  
  
  RESULTS
  Among the approximately 60,000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value = .004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value = .02).
  
  
  CONCLUSIONS
  A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.
authors: Division of Genetic Basis of Human Disease, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors: David
authors: D
authors: Duggan
authors: Siqun L
authors: SL
authors: Zheng
authors: Michele
authors: M
authors: Knowlton
authors: Debbie
authors: D
authors: Benitez
authors: Latchezar
authors: L
authors: Dimitrov
authors: Fredrik
authors: F
authors: Wiklund
authors: Christiane
authors: C
authors: Robbins
authors: Sarah D
authors: SD
authors: Isaacs
authors: Yu
authors: Y
authors: Cheng
authors: Ge
authors: G
authors: Li
authors: Jielin
authors: J
authors: Sun
authors: Bao-Li
authors: BL
authors: Chang
authors: Leslie
authors: L
authors: Marovich
authors: Kathleen E
authors: KE
authors: Wiley
authors: Katarina
authors: K
authors: Bälter
authors: Pär
authors: P
authors: Stattin
authors: Hans-Olov
authors: HO
authors: Adami
authors: Marta
authors: M
authors: Gielzak
authors: Guifang
authors: G
authors: Yan
authors: Jurga
authors: J
authors: Sauvageot
authors: Wennuan
authors: W
authors: Liu
authors: Jin Woo
authors: JW
authors: Kim
authors: Eugene R
authors: ER
authors: Bleecker
authors: Deborah A
authors: DA
authors: Meyers
authors: Bruce J
authors: BJ
authors: Trock
authors: Alan W
authors: AW
authors: Partin
authors: Patrick C
authors: PC
authors: Walsh
authors: William B
authors: WB
authors: Isaacs
authors: Henrik
authors: H
authors: Grönberg
authors: Jianfeng
authors: J
authors: Xu
authors: John D
authors: JD
authors: Carpten
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden; D044465:White People / Q000235:genetics*; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C462952:DAB2IP protein, human; D020703:ras GTPase-Activating Proteins