title: A novel founder mutation in the RNASEL gene, 471delAAAG, is associated with prostate cancer in Ashkenazi Jews.
abstract: HPC1/RNASEL was recently identified as a candidate gene for hereditary prostate cancer. We identified a novel founder frameshift mutation in RNASEL, 471delAAAG, in Ashkenazi Jews. The mutation frequency in the Ashkenazi population, estimated on the basis of the frequency in 150 healthy young women, was 4% (95% confidence interval [CI] 1.9%-8.4%). Among Ashkenazi Jews, the mutation frequency was higher in patients with prostate cancer (PRCA) than in elderly male control individuals (6.9% vs. 2.4%; odds ratio = 3.0; 95% CI 0.6-15.3; P=.17). 471delAAAG was not detected in the 134 non-Ashkenazi patients with PRCA and control individuals tested. The median age at PRCA diagnosis did not differ significantly between the Ashkenazi carriers and noncarriers included in our study. However, carriers received diagnoses at a significantly earlier age, compared with patients with PRCA who were registered in the Israeli National Cancer Registry (65 vs. 74.4 years, respectively; P<.001). When we examined two brothers with PRCA, we found a heterozygous 471delAAAG mutation in one and a homozygous mutation in the other. Loss of heterozygosity was demonstrated in the tumor of the heterozygous sib. Taken together, these data suggest that the 471delAAAG null mutation is associated with PRCA in Ashkenazi men. However, additional studies are required to determine whether this mutation confers increased risk for PRCA in this population.
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, Israel.
authors.forename: Hanna
authors.initials: H
authors.lastname: Rennert
authors.forename: Dani
authors.initials: D
authors.lastname: Bercovich
authors.forename: Ayala
authors.initials: A
authors.lastname: Hubert
authors.forename: Dvora
authors.initials: D
authors.lastname: Abeliovich
authors.forename: Uri
authors.initials: U
authors.lastname: Rozovsky
authors.forename: Anat
authors.initials: A
authors.lastname: Bar-Shira
authors.forename: Sonya
authors.initials: S
authors.lastname: Soloviov
authors.forename: Letizia
authors.initials: L
authors.lastname: Schreiber
authors.forename: Haim
authors.initials: H
authors.lastname: Matzkin
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.forename: Luna
authors.initials: L
authors.lastname: Kadouri
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
authors.forename: Yuval
authors.initials: Y
authors.lastname: Yaron
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
mesh_terms: D000954:Antigens, Surface / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D050827:Syntaxin 1
chemical_list: D000954:Antigens, Surface; D009419:Nerve Tissue Proteins; D050827:Syntaxin 1