BRCA1/BRCA2基因突变的乳腺癌患者特征分析

目的对钱塘江南岸地区BRCA1/BRCA2基因突变的乳腺癌患者特征进行分析,为国家及各地公共卫生主管部门制定乳腺癌防治方案奠定基础。方法选取2016年来萧山医院就诊18周岁以上女性由乳腺钼靶摄影或乳腺彩超及由病理学诊断为乳腺癌的98例患者,通过PCR和测序分析对BRCA1/BRCA2基因突变进行分析,对乳腺癌患者进行相关肿瘤标志物的检测,采用问卷调查的方式对乳腺癌患者进行流行病学调查。结果通过对98例乳腺癌患者BRCA1/2基因全外显子以及外显子内含子拼接区序列测序,共发现23例BRCA2基因缺失突变,所有突变位点均为首次发现。BRCA1/2基因突变乳腺癌患者相关肿瘤标志物具有一定差异。BRCA1/2基因突变的乳腺癌患者主要以中年妇女为主,此外与乳腺癌相关的疾病史对于BRCA1/2基因的突变也具有一定意义。结论钱塘江南岸地区的女性乳腺癌患者中BRCA1/BRCA2基因突变频率较高,且以中年妇女为主,应定期进行随访监测。     

BRCA1基因与乳腺癌研究进展

乳腺癌易感基因BRCA1作为抑癌基因 ,其编码产物在细胞周期调控、DNA损伤修复以及肿瘤细胞的凋亡中扮演着重要角色。大量研究证明 ,BRCA1基因结构、功能异常与乳腺癌的发生发展有十分密切的联系。本文拟就BRCA1与乳腺癌相关研究的最新进展作一综述     

115 BRCA1基因与乳腺癌研究进展

乳腺癌易感基因BRCA1作为抑癌基因,其编码产物在细胞周期调控、DNA损伤修复以及肿瘤细胞的凋亡中扮演着重要角色.大量研究证明,BRCA1基因结构、功能异常与乳腺癌的发生发展有十分密切的联系.本文拟就BRCA1与乳腺癌相关研究的最新进展作一综述.     

乳腺癌中BRCA1基因突变与雌激素受体的关系

目的探讨遗传性乳腺癌与卵巢癌易感基因(Hereditarybreastandovariancancersusceptibilitygene,BRCA1)基因突变、雌激素受体(Estrogenreceptor,ER)在乳腺癌中的作用以及二者之间的关系。方法选取64例乳腺癌患者标本作研究组,另取10例非癌乳腺组织标本作对照组。利用PCR-SSCP法和直接测序法检测BRCA1基因突变情况;利用SP(链霉菌抗生物素蛋白-过氧化物酶链接法)二步法检测ER,比较ER阳性组与ER阴性组BRCA1突变情况。结果10例非乳腺癌组织未检测出BRCA1基因突变。64例乳腺癌标本中检出BRCA1基因突变6例,突变率为9.4%。突变发生在5、12、17外显子上,均为错义突变,ER阳性44例,阳性率为68.75%(44/64)。ER阳性组中只有1例BRCA1突变(1/44),ER阴性组中有5例检出BRCA1突变(5/20),两组比较BRCA1突变率有显著差异性(P>0.05)。结论广西乳腺癌与BRCA1基因突变有关,BRCA1突变与雌激素受体有关,BRCA1基因突变病人雌激素阴性状态比非BRCA1基因突变病人多。     

朝鲜族和汉族妇女乳腺癌BRCA1的表达及临床意义

目的:探讨BRCA1基因蛋白在延边地区朝鲜族、汉族(简称朝、汉族)妇女乳腺癌中的表达及意义。方法:采用免疫组化SP法对72例乳腺癌(35例朝鲜族,37例汉族)、15例乳腺纤维腺瘤组织石蜡切片进行BRCA1检测,分析与临床病理特征的关系。结果:BRCA1蛋白在朝、汉族妇女乳腺癌病人中的表达率分别为62.9%、56.8%;在乳腺癌、乳腺纤维腺瘤组织中的表达率分别为59.7%和100%,乳腺癌组织中BRCA1基因表达水平低于良性肿瘤组织(P<0.05);乳腺癌组织中BRCA1的表达与组织学分级呈负相关(r=-0.418,P<0.05),与淋巴结转移数目、患者年龄及家族史均无明显相关。结论:BRCA1在朝、汉族妇女乳腺癌中的表达无显著性差异;其表达水平的下调在乳腺癌发生发展中有重要意义;表达的减弱与乳腺癌的病理学分级有关,提示预后差。     

维吾尔族及汉族乳腺癌BRCA1基因突变检测及分析

[目的]研究新疆地区维吾尔族及汉族乳腺癌患者BRCA1基因(乳腺癌易感基因1)突变情况及突变位置。[方法]选取维吾尔族及汉族乳腺癌根治标本110例,对照组为32例维吾尔族及汉族乳腺良性病变(纤维腺病及纤维腺瘤)及乳腺癌旁非癌组织;运用PCR-SSCP和DNA序列测定的方法检测BRCA1基因的突变。[结果](1)110例维吾尔族及汉族散发性乳腺癌中BRCA1的突变率为10%;其中70例维吾尔族散发性乳腺癌BRCA1的突变率为12.86%;新疆早发性乳腺癌(≤35岁)中BRCA1基因的突变率高于新疆晚发性乳腺癌,差异有统计学意义(χ2=9.429,P﹤0.01)。维吾尔族早发性乳腺癌BRCA1突变率高于维吾尔族晚发性乳腺癌,差异有统计学意义(χ2=10.295,P﹤0.01)。(2)2例双侧乳腺癌中均检测出BRCA1基因的突变。(3)对照组32例维吾尔族及汉族乳腺癌旁非癌组织及乳腺良性病变中仅发现1例BRCA1基因核苷酸的多态性,110例新疆散发性乳腺癌中发现11例BRCA1基因核苷酸的多态性。[结论]BRCA1突变可能与新疆早发性乳腺癌尤其是维吾尔族早发性乳腺癌及双侧乳腺癌的发生密切相关。     

银屑病患者的环境因素与HLA-DQA1等位基因关联研究

目的研究Ⅰ型银屑病环境因素与HLA-DQA1等位基因之间的交互作用.方法采用病例对照研究方法,调查了144例Ⅰ型银屑病患者和273名健康人的环境因素;用序列特异性引物PCR(PCR-SSP)方法检测HLA-DQA1等位基因,对Ⅰ型银屑病的环境因素与HLA-DQA1等位基因间交互作用进行了研究.结果 (1)HLA-DQA1*0104和DQA1*0201与Ⅰ型银屑病患者存在正相关性(Pc＜0.002);HLA-DQA1*0501与Ⅰ型银屑病患者存在负相关(Pc＜0.000 5).(2)HLA-DQA1*0104等位基因与受潮(P=0.023 8,OR=5.29)存在交互作用.(3)HLA-DQA1*0201等位基因与10个环境因素无交互作用.(4)HLA-DQA1*0501等位基因与受潮(P=0.002 4,OR=7.50)、食鱼虾(P=0.000 4,OR=12.92)、药物(P=0.043 3,OR=9.43)和接种疫苗(P=0.043 3,OR=9.43)存在交互作用. 结论 (1)HLA-DQA1*0104和DQA1*0201可能是Ⅰ型银屑病的易感基因或与易感基因相连锁;HLA-DQA1*0501等位基因可能具有阻止汉族人发生Ⅰ型银屑病的作用.(2)HLA-DQA1*0104和DQA1*0501等位基因能增加环境危险因素发生Ⅰ型银屑病的危险性.     

乳腺癌易感基因1在乳腺肿瘤中的表达及其意义

目的：研究乳腺癌易感基因1（BRCA1）在散发性乳腺癌和乳腺良性肿瘤中的表达及其临床意义。方法：应用SABC免疫组化法检测30例乳腺纤维腺瘤、42例乳腺癌中BRCAI的表达。结果：BRCA1在乳腺纤维腺瘤中的阳性表达率86．7％，在乳腺癌中为52．4％，腋窝有淋巴结转移组的表达率明显低于无淋巴结转移组（P〈0．05），随着肿瘤分级的升高BRCA1的阳性表达率有逐渐下降趋势，其中Ⅰ级和Ⅲ级、Ⅱ级和Ⅲ级间的差异有统计学意义（P〈0．05），BRCA1的表达与肿瘤的组织学类型、肿块大小无关（均P〉0．05）。结论：BRCA1在乳腺癌的发生发展过程中有重要的作用，它有可能成为临床对乳腺癌诊断和判断预后的一个重要指标。     

应用下一代测序技术检测BRCA1/2及同源重组修复通路多基因胚系突变及相关性分析

目的:应用下一代测序（next-generation sequencing,NGS）技术检测乳腺癌患者及高风险个体胚系基因突变,分析同源重组修复（homologous recombination repair,HR）通路基因突变状态与乳腺癌临床病理特征的相关性,以补充中国乳腺癌相关基因突变数据库。方法:本研究为横断面研...     

湖南汉族MICA＊008／A5．1等位基因的调查分析

目的 调查湖南汉族群体MICA＊008／A5．1等位基因的频率分布。方法 应用PCR／SSP技术对81名无血缘关系的湖南汉族健康个体作MICA＊008／A5．1等位基因检测。结果 检测出MICA＊008／A5．1等位基因的频率为56.8％。结论 湖南汉族群体MICA＊008／A5．1等位基因频率较高，并提供了湖南汉族群体MICA＊008／A5．1等值基因频率的正常参考值。     

BRCA1和BRCA2在乳腺疾病中的表达和意义

目的通过检测乳腺癌易感基因1(BRCA1)和乳腺癌易感基因2(BRCA2)在乳腺增生病、乳腺癌癌前病变、乳腺癌中的表达,探讨BRCA1和BRCA2在乳腺癌发生、发展中的作用。方法切除的原发病灶共90例,经福尔马林固定、石蜡包埋,常规切片,应用免疫组织化学技术(IHC),检测乳腺增生病、乳腺癌癌前病变、乳腺癌中的BRCA1和BRCA2表达情况。结果(1)BRCA1和BRCA2在乳腺增生病、乳腺癌癌前病变、乳腺癌中阳性表达率依次递减,在三者中的表达有显著性差异(P<0.05)。(2)BRCA1和BRCA2的表达相互之间无显著性差异(P>0.05)。结论乳腺上皮中BRCA1和BRCA2的表达减少对乳腺癌的发生、发展具有重要作用。对BRCA1和BRCA2的检测有利于筛选出乳腺癌高危人群,早期发现乳腺癌。但BRCA1和BRCA2在乳腺癌中的表达无相关性。     

BRCA1 R841W: A strong candidate for a common mutation with moderate phenotype

BRCA1 mutations cause increased risk for breast and ovarian cancer, frequently of early onset. Many different mutations occur in BRCA1, including several examples of recurrent mutations, each of which accounts for a significant number of families with heritable cancer predisposition. These common mutations have an etiological role in many breast and ovarian cancer cases and provide the opportunity to examine genotype-phenotype correlations and genotype-environment interactions in individuals with the identical BRCA1 lesion. We report a novel missense change in BRCA1, 2640 C→T (R841W), found in 3 cases from a subject group of 305 breast and 79 ovarian cancer cases from Orange County, CA. These are consecutive, population-based cases not selected for age or family history. In all three cases, there is a strong family history of breast, ovarian, or other cancers possibly related to a BRCA1 defect and family members showed a high concordance of cancer incidence with the presence of R841W. The age of cancer onset was not always distinct from typical sporadic cases. Testing of a sample of 413 unrelated individuals to examine the hypothesis that R841W might be a rare polymorphism detected one additional instance in a woman with breast cancer diagnosed at age 77 years, and cancer in one parent. R841W is likely to be an etiologically significant lesion with involvement in close to 1% (95% confidence interval 0–1.7%) of all breast and ovarian cancers in this population. © 1996 Wiley-Liss, Inc.     

Estimating the number of potential family members eligible for BRCA1 and BRCA2 mutation testing in a “Traceback” approach

U.S. guidelines recommend BRCA1/2 mutation testing for women diagnosed with high‐grade ovarian cancer (HGOC) to increase recognition of carriers, but most remain unidentified and at risk. Accordingly, an approach termed “Traceback” has been proposed in which probands are retrospectively identified by testing archived pathology specimens, and family members are traced to provide genetic counseling and testing. We used population‐based data to estimate the number of family members who might be contacted through such a program. We used incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program to estimate the number of women diagnosed with HGOC from 2005 to 2016, and census data to estimate the number of spouses, offspring, and siblings (both sexes). Using overall survival for HGOC from SEER and all‐cause mortality rates from the Centers for Diseases Control and Prevention, we estimated the number of patients, spouses, offspring, and siblings of HGOC cases living in 2017. Due to the high mortality rate of HGOC, consent from living probands may be possible in only 42% of the cases; consent to test pathology specimens would need to be sought from next of kin for the remainder. In 2017, an estimated 406,919 living next of kin (spouses, siblings, offspring) would be available for potential consent. Testing archived ovarian cancer pathology specimens may enable the identification of BRCA1/2 mutation carriers, but consent from next of kin would be required in in 58% of cases. Although Traceback offers the possibility of identifying unaffected BRCA1/2 mutation carriers, pilot feasibility studies that include assessment of methods to secure consent are needed.     

A Cost-Effectiveness Evaluation of Germline BRCA1 and BRCA2 Testing in UK Women with Ovarian Cancer

Objectives

To evaluate the long-term cost-effectiveness of germline BRCA1 and BRCA2 (collectively termed “BRCA”) testing in women with epithelial ovarian cancer, and testing for the relevant mutation in first- and second-degree relatives of BRCA mutation–positive individuals, compared with no testing. Female BRCA mutation–positive relatives of patients with ovarian cancer could undergo risk-reducing mastectomy and/or bilateral salpingo-oophorectomy.

The cost-utility of magnetic resonance imaging for breast cancer in BRCA1 mutation carriers aged 30–49

Recent evidence has investigated the cost-effectiveness of magnetic resonance imaging (MRI) in younger women with a BRCA1 mutation. However, this evidence has not been contrasted with existing cost-effectiveness standards to determine whether screening is appropriate, given limited societal resources. We constructed a Markov model investigating surveillance tools (mammography, MRI, both in parallel) under a National Health Service (NHS) perspective. The key benefit of MRI is that increased sensitivity leads to early detection, and improved prognosis. For a 30- to 39-year-old cohort, the cost per quality-adjusted life year (QALY) of mammography relative to no screening was ￡5,200. The addition of MRI to this costs ￡13,486 per QALY. For a 40- to 49-year-old cohort, the corresponding values were ￡2,913 and ￡7,781. Probabilistic sensitivity analysis supported the cost-effectiveness of the parallel approach of mammography and MRI. It is necessary to extend this analysis beyond BRCA1 carriers within this age group, and also to other age groups.     

维、汉族乳腺癌中BRCA1、P53及Ki-67蛋白的表达

[目的]研究维吾尔族及汉族乳腺癌患者中BRCA1、P53及Ki-67蛋白的表达及其意义.[方法]选取100例维吾尔族和25例汉族乳腺癌根治标本,对照组为126例维汉族乳腺良性病变(纤维腺病及纤维腺瘤)及乳腺癌旁非癌组织;运用免疫组化Evision二步法检测BRCA1、P53及Ki-67蛋白的表达.[结果](1)在乳腺良性病变及乳腺癌旁非癌组织中,BRCA1蛋白均定位于细胞核内.在乳腺癌组织中,93例完全表达为细胞浆阳性,阳性率为74.4%,32例表达缺失.(2)BRCA1蛋白的表达与组织学分级、患者的年龄、淋巴结转移及民族有明显相关性(P ＜0.05).(3)乳腺癌中P53蛋白和Ki-67的表达呈正相关(P＜0.01);BRCA1蛋白与P53及Ki-67的表达呈负相关(P＜0.01).(4)乳腺癌中P53及Ki-67蛋白的阳性表达率(53.6%;28.92±16.90)明显高于乳腺良性病变(1.59%,5.38±3.43)(P＜0.01).[结论]BRCA1蛋白、P53和Ki-67蛋白阳性表达可能在乳腺良性病变恶性转化及乳腺癌的发生中具有重要作用,有可能成为临床预测预后的重要指标之一.