Rare germline mutations in African American men diagnosed with early-onset prostate cancer
Rare germline mutations in African American men diagnosed with early-onset prostate cancer
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DOI：
10.1002/pros.23464
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发表时间：
2018-04-01
期刊：
影响因子：
2.8
通讯作者：
Cooney, Kathleen A.
中科院分区：
文献类型：
--
作者：
Beebe-Dimmer, Jennifer L.;Zuhlke, Kimberly A.;Cooney, Kathleen A.
背景与非西班牙裔白人相比，非裔美国人的前列腺癌发病率和疾病特异性死亡率更高。从历史上看，对非洲裔美国男性前列腺癌的罕见遗传变异贡献的调查一直受到大型遗传研究参与率低的阻碍，特别是那些集中在早发性和家族性疾病。方法我们测序了160个基因，据称是参与生殖系DNA样本中的致癌途径，从96名非洲裔美国男性诊断为早发性前列腺癌（诊断时55岁）。REVEL软件被用来确定观察到的错义variants.ResultsWe观察到三个蛋白质截短突变，一个在BRCA 2和两个BRIP 1在三个非洲裔美国男性诊断为早发性前列腺癌的致病潜力。此外，我们观察到五种罕见的，大多是私人的，错义变异的四个基因（BRCA1，BRCA2，PMS2和ATM），被预测为有害的，因此可能致病在我们的患者sample.ConclusionsProtein截断突变BRCA2和BRIP1被发现在非洲裔美国男性诊断为早发性前列腺癌。有必要进一步研究以确定罕见的错义变异对前列腺癌发病率的作用，以及这组高危男性的进展。
BackgroundAfrican Americans have both a higher incidence of prostate cancer and greater disease-specific mortality compared with non-Hispanic whites. Historically, the investigation of the contribution of rare genetic variants to prostate cancer in African American men has been hampered by low participation in large genetic studies, particularly those focused on early-onset and familial disease.MethodsWe sequenced 160 genes purported to be involved in carcinogenic pathways in germline DNA samples collected from 96 African American men diagnosed with early-onset prostate cancer (55 years at diagnosis). REVEL software was used to determine the pathogenic potential of observed missense variants.ResultsWe observed three protein-truncating mutations, one in BRCA2 and two in BRIP1 in three African American men diagnosed with early-onset prostate cancer. Furthermore, we observed five rare, mostly private, missense variants among four genes (BRCA1, BRCA2, PMS2, and ATM) that were predicted to be deleterious and hence likely pathogenic in our patient sample.ConclusionsProtein-truncating mutations in BRCA2 and BRIP1 were discovered in African American men diagnosed with early-onset prostate cancer. Further study is necessary to determine the role of rare, missense variants to prostate cancer incidence, and progression in this group of high-risk men.