RNASEL mutation screening and association study in Ashkenazi and non-Ashkenazi prostate cancer patients.
Epidemiologic and genetic studies support the considerable effect of heritable factors on prostate tumorigenesis, although to date, no unequivocal susceptibility gene has been identified. The extensive study of RNASEL in prostate cancer patients worldwide has yielded conflicting results. We reevaluated the role of the RNASEL 471delAAAG Ashkenazi founder mutation in 1,642 Ashkenazi patients with prostate, bladder, breast/ovarian, and colon cancers; Ashkenazi controls; and in non-Ashkenazi prostate cancer patients and controls. The entire RNASEL coding sequence was also screened using denaturing high-performance liquid chromatography and multiplex ligation-dependent probe amplification for possible sequence variations or copy number changes in a population of prostate cancer patients. The 471delAAAG mutation was detected in 2.4% of the Ashkenazi prostate cancer patients; in 1.9% of patients with bladder, breast/ovarian, and colon cancers; and in 2.0% of the Ashkenazi controls. Seven additional variants were detected in RNASEL, including a novel potentially pathogenic splice site mutation, IVS5+1delG, although none were associated with increased prostate cancer risk. Multiplex ligation-dependent probe amplification analysis showed two RNASEL gene copies in all 300 prostate cancer patients tested. We estimated that the RNASEL 471delAAAG founder mutation, which was detected in 2% of the Ashkenazi Jews, originated between the 2nd and 5th centuries A.D., compared with the less frequent (1%) BRCA1 185delAG founder mutation, which originated hundreds of years earlier. Taken together, our analysis does not support a role for the RNASEL 471delAAAG Ashkenazi mutation nor for the other alterations detected in RNASEL in prostate cancer risk in Jewish men.
Orr-Urtreger
Avi
A
Genetic Institute, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, 64239 Tel Aviv, Israel. aviorr@tasmc.health.gov.il
Bar-Shira
Anat
A
Bercovich
Dani
D
Matarasso
Noa
N
Rozovsky
Uri
U
Rosner
Serena
S
Soloviov
Sonya
S
Rennert
Gad
G
Kadouri
Luna
L
Hubert
Ayala
A
Rennert
Hanna
H
Matzkin
Haim
H
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011336:Probability; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D012016:Reference Values; D012260:Ribonucleases / Q000235:genetics*
D012260:Ribonucleases