Wilkens E P, Freije D, Xu J, Nusskern D R, Suzuki H, Isaacs S D, Wiley K, Bujnovsky P, Meyers D A, Walsh P C, Isaacs W B
James Buchanan Brady Urologic Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Prostate. 1999 Jun 1;39(4):280-4. doi: 10.1002/(sici)1097-0045(19990601)39:4<280::aid-pros8>3.0.co;2-f.
Two genes responsible for hereditary breast cancer (BRCA1 and BRCA2) have been identified, and predisposing mutations identified. Several studies have provided evidence that germline mutations in BRCA1 and BRCA2 confer an increased risk of prostate cancer. Based on these findings, one might expect to find an increased frequency of mutations in these genes in family clusters of prostate cancer. The Ashkenazi Jewish population is unique in that it has an approximate 2% incidence of specific founder BRCA1 and BRCA2 mutations (i.e., 185delAG and 5382insC in BRCA1, and 6174delT in BRCA2).
To address the question of whether or not mutations in either of these genes were overrepresented in prostate cancer families, we searched for these mutations in germline DNA samples collected from affected and unaffected members of 18 Ashkenazi Jewish families, each having at least 3 first-degree relatives affected with prostate cancer.
No mutations were found in the BRCA1 gene in any of the 47 individuals tested. One individual possessed a BRCA2 mutation (6174delT). This individual was unaffected at the time of analysis, but had an affected paternal uncle, and an affected first cousin, neither of whom harbored the mutant gene.
In this sample of Ashkenazi prostate cancer families, the frequency of founder BRCA1 and BRCA2 mutations was not elevated, suggesting that such mutations will account for only a small, perhaps minimal, fraction of familial prostate cancer.
已鉴定出两个与遗传性乳腺癌相关的基因（BRCA1和BRCA2），并确定了易感性突变。多项研究已提供证据表明，BRCA1和BRCA2中的种系突变会增加患前列腺癌的风险。基于这些发现，人们可能会预期在前列腺癌家族聚集人群中这些基因的突变频率会增加。阿什肯纳兹犹太人群体具有独特性，因为其特定的BRCA1和BRCA2奠基者突变发生率约为2%（即BRCA1中的185delAG和5382insC，以及BRCA2中的6174delT）。
为了探讨这两个基因中的任何一个突变在前列腺癌家族中是否过度存在，我们在从18个阿什肯纳兹犹太家族的患病和未患病成员收集的种系DNA样本中寻找这些突变，每个家族至少有3名患前列腺癌的一级亲属。
在检测的47个人中，未在任何一个人身上发现BRCA1基因突变。有一个人携带BRCA2突变（6174delT）。该个体在分析时未患病，但有一个患病的叔伯和一个患病的堂兄，他们都未携带该突变基因。
在这个阿什肯纳兹前列腺癌家族样本中，BRCA1和BRCA2奠基者突变的频率没有升高，这表明此类突变在家族性前列腺癌中仅占一小部分，也许是极小的一部分。
