Mutation analysis of BRIP1 in male breast cancer cases: a population-based study in Central Italy
Mutation analysis of BRIP1 in male breast cancer cases: a population-based study in Central Italy
复制标题
DOI：
10.1007/s10549-010-1289-x
复制
发表时间：
2011-04-01
影响因子：
3.8
通讯作者：
Ottini, Laura
中科院分区：
文献类型：
--
作者：
Silvestri, Valentina;Rizzolo, Piera;Ottini, Laura
男性乳腺癌（BC）与女性相比是罕见的，但随着人们对这种罕见疾病的关注，其发病率正在增加。尽管存在一些差异，但男性和女性BC具有相似的遗传易感因素，包括BRCA1/2、CHEK2和PALB2突变。与其他BRCA1/2功能相关的DNA修复基因（如CHEK2和PALB2）一样，BRIP1被认为是一个中等外显率的BC易感基因。目前，BRIP1在男性BC易感性中的作用尚不清楚。在这项研究中，我们旨在评估BRIP1变异是否可能导致男性BC （MBC）风险，通过筛选97例MBC病例，这些病例均为BRCA1/2、CHEK2和PALB2突变阴性，这些病例来自意大利中部的126例MBC人群。在我们的系列中共检测到5个BRIP1种系序列改变，3个编码变异和2个非编码变异。两个非编码变异IVS4-28G > A和3'UTR 4049C > T通过硅分析被归类为中性。3个编码变异体中，1个是沉默变异体（E879E）， 2个是氨基酸取代变异体（R264W和P919S），通过硅分析推测其致病作用。然而，进一步分析肿瘤相关的杂合性缺失和变异等位基因的频率，在203个男性人群对照中进行测试，表明这两种变异的影响都是中性的。总的来说，我们的结果表明BRIP1变异可能在MBC易感性中不起相关作用。
Breast cancer (BC) in men is rare compared with BC in women, but its incidence is increasing along with attention toward this uncommon disease. Although with some differences, male and female BC share similar genetic predisposition factors, including BRCA1/2, CHEK2, and PALB2 mutations. As other BRCA1/2 functionally related DNA repair genes, such as CHEK2 and PALB2, BRIP1 is considered a moderate-penetrance BC susceptibility gene. At present, the role of BRIP1 on BC susceptibility in men is unknown. In this study, we aimed to assess whether BRIP1 variants may contribute to male BC (MBC) risk, by screening 97 MBC cases, all negative for BRCA1/2, CHEK2, and PALB2 mutations, selected from a population-based series of 126 MBCs from Central Italy. A total of five BRIP1 germ-line sequence alterations, three coding, and two non-coding variants, were detected in our series. The two non-coding variants IVS4-28G > A and 3'UTR 4049C > T were classified as neutral by in silico analysis. Of the three coding variants, one was a silent variant (E879E) and two resulted in amino acid substitution (R264W and P919S) showing a putative pathogenic role by in silico analysis. However, further analysis of tumor-associated loss of heterozygosity and the frequency of variant alleles, tested in 203 male population controls, suggested a neutral effect for both of these variants. Overall, our results indicate that BRIP1 variants may not play a relevant role in MBC predisposition.