title: Contribution of HPC1 (RNASEL) and HPCX variants to prostate cancer in a founder population.
abstract: BACKGROUND
  Prostate cancer is a genetically complex disease with locus and disease heterogeneity. The RNASEL gene and HPCX locus have been implicated in hereditary prostate cancer; however, their contributions to sporadic forms of this malignancy remain uncertain.
  
  
  METHODS
  Associations of prostate cancer with two variants in the RNASEL gene (a founder mutation, 471delAAAG, and a non-synonymous SNP, rs486907), and with five microsatellite markers in the HPCX locus, were examined in 979 cases and 1,251 controls of Ashkenazi Jewish descent. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models.
  
  
  RESULTS
  There was an inverse association between RNASEL rs486907 and prostate cancer in younger men (<65 years) and those with a first-degree relative with prostate cancer; men with AA genotype had ORs of 0.64 and 0.47 (both P < 0.05), respectively, in comparison to men with GG genotype. Within the HPCX region, there were positive associations for allele 135 of bG82i1.1 marker (OR = 1.77, P = 0.01) and allele 188 of DXS1205 (OR = 1.65, P = 0.02). In addition, allele 248 of marker D33 was inversely associated (OR = 0.65, P = 0.05) with Gleason score ≥7 tumors.
  
  
  CONCLUSIONS
  Results suggest that variants in RNASEL contribute to susceptibility to early onset and familial forms of prostate cancer, whereas HPCX variants are associated with prostate cancer risk and tumor aggressiveness. The observation that a mutation predicted to completely inactivate RNASEL protein was not associated with prostate cancer, but that a missense variant was associated, suggests that the effect is due to either partial inactivation of the protein, and/or acquisition of a new protein activity.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Ilir
authors.initials: I
authors.lastname: Agalliu
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leanza
authors.forename: Lorie
authors.initials: L
authors.lastname: Smith
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Trent
authors.forename: John D
authors.initials: JD
authors.lastname: Carpten
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004722:Endoribonucleases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007585:Jews; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease