RNASEL mutation screening and association study in Ashkenazi and non-Ashkenazi prostate cancer patients
RNASEL mutation screening and association study in Ashkenazi and non-Ashkenazi prostate cancer patients
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DOI：
10.1158/1055-9965.epi-05-0606
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发表时间：
2006-03-01
影响因子：
3.8
通讯作者：
Matzkin, H
中科院分区：
文献类型：
--
作者：
Orr-Urtreger, A;Bar-Shira, A;Matzkin, H
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 founded 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 founded mutation, which originated hundreds of years earlier. Taker together, our analysis does not support a role for the RNASEL 471delAAAG Ashkenazi mutation nor for the other alter ations detected in RNASEL in prostate cancer risk in jewish men.
