乳腺癌分子遗传学研究进展

乳腺癌易感基因的研究对有乳腺癌家族史的个体进行早诊和预防、阐明散发性乳腺癌发病机制、早诊、判断药物敏感性和预后、鉴别诊断良恶性疾病等均有重要意义.BRCA1和BRCA2是乳腺癌主要易感基因.其他易感基因诸如TP53能增加BRCA1、BRCA2的乳腺癌患病风险.     

乳腺癌分子遗传学研究进展

乳腺癌易感基因的研究对有乳腺癌家族史的个体进行早诊和预防、阐明散发性乳腺癌发病机制、早诊、判断药物敏感性和预后、鉴别诊断良恶性疾病等均有重要意义.BRCA1和BRCA2是乳腺癌主要易感基因.其他易感基因诸如TP53能增加BRCA1、BRCA2的乳腺癌患病风险.     

乳腺癌BRCA1、BRCA2基因突变及其临床应用

乳腺癌的发生与遗传因素密切相关.研究表明,乳腺癌易感基因(BRCA)1、2在乳腺癌的发生、发展过程中具有重要作用,针对BRCA基因突变的研究对乳腺癌的预防、诊断及治疗具有重要意义.     

散发性甲状腺癌中BRCA1和BRCA2的表达情况

目的 探讨乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)和乳腺癌易感基因2(breast canc-er susceptibility gene 2,BRCA2)在散发性甲状腺癌中的表达和意义.方法 应用免疫组化法,检测散发性甲状腺癌中BRCA1和BRCA2的表达...     

乳腺癌易感基因BRCA1和BRCA2的突变检测及其临床意义

乳腺癌易感基因BRCA1、BRCA2在家族性和遗传性乳腺癌中突变率较高。现就其功能、检测及临床应用方面的研究进展作一综述。     

乳腺癌易感基因1的临床研究进展

乳腺癌易感基因1(BRCA1)突变与乳腺癌、卵巢癌等许多癌症发生密切相关.近年来越来越多的研究提示,在化疗疗效、放疗敏感性及手术效果等方面,BRCA1突变乳腺癌与其他乳腺癌相比有显著差异.BRCA1的研究为其今后在临床上的应用提供了方向.     

BRCA1和BRCA2基因与乳腺癌相关的研究进展

BRCA1和BRCA2基因是与乳腺癌尤其是遗传性乳腺癌发生发展密切相关的抑癌基因.研究表明,部分乳腺癌患者存在BRCA1和BRCA2基凶突变,而且出现这两个基因突变的乳腺癌表现出不同的病理学特点.通过检测乳腺癌患者BRCA1和BRCA2基因的突变情况,将有助于对乳腺癌患者预后的早期评估.     

乳腺癌易感基因的研究进展

随着乳腺癌发病率逐年的增加,对乳腺癌的易感基因的研究越来越受到重视,通过乳腺癌易感基因的研究。对有乳腺癌家族史的个体进行早期诊断和预防,对阐明散发性乳腺癌的发病机理,早期诊断和判断预后,药物敏感性。良恶性疾病的鉴别诊断有重要意义。人们对高外显率的乳腺癌易感基因BRCA1,BRCA2等的研究较多,但对一些低外显率的易感基因如参与激素代谢的酶类基因CYP家族成员（CYP17,CYP19,CYP1A1等）参与致癌物代谢的基因（GSTM1,NAT1,NAT2）和DNA损伤修复基因（ATM）等了解较少,本文就目前发现的乳腺癌常见易感基因研究现状作一综述。     

乳腺癌BRCA1/2基因大片段重排的研究进展北大核心CSCD

乳腺癌是女性最常见的恶性肿瘤,BRCA1与BRCA2是乳腺癌最重要的易感基因,携带BRCA1/2胚系突变的女性,其乳腺癌的终身患病风险显著增高。BRCA1/2致病性突变多为单个或数个碱基改变引起的移码突变和无义突变,但常规的Sanger测序筛查方法尚不足以发现BRCA1/2其他胚系缺陷类型,如大片段重排。随着基因检测方法的进步,多种BRCA1/2基因重排被发现,在遗传性乳腺癌家族接受常规BRCA1/2基因测序未发现突变的情况下,应认真考虑检测大片段重排,以免漏诊。     

38例散发乳腺癌患者BRCA1基因突变检测

肿瘤易感基因BRCA1(breast and ovarian canoer suscepti-bility gene,BRCA1)与乳腺癌,卵巢癌发生有密切联系,它的失活可导致细胞的恶性转化和肿瘤的发生.BRCA1基因突变者患癌的风险远高于普通群体,对于有家族史的高危人群中筛查BRCA1基因,对于乳腺癌卵巢癌患者风险评估,发病检测,早期诊断及今后的基因治疗等都有很重要的临床意义.     

乳腺癌中BRCA1基因突变与雌激素受体研究进展

乳腺癌的发生是一系列基因改变的结果。BRCA1是遗传性乳腺癌易感基因，其结构、功能异常与乳腺癌的发生发展有十分密切的联系。雌激素受体（ER）作为乳腺癌的生物学标志物，是目前较为可靠的指导治疗和判定预后的重要指标。研究乳腺癌中BRCA1基因突变与雌激素受体的关系，对阐明乳腺癌的发病机制、早期诊断及治疗有意义。     

乳腺癌中BRCA1基因突变与雌激素受体研究进展

乳腺癌的发生是一系列基因改变的结果。BRCA1是遗传性乳腺癌易感基因,其结构、功能异常与乳腺癌的发生发展有十分密切的联系。雌激素受体(ER)作为乳腺癌的生物学标志物,是目前较为可靠的指导治疗和判定预后的重要指标。研究乳腺癌中BRCA1基因突变与雌激素受体的关系,对阐明乳腺癌的发病机制、早期诊断及治疗有意义。     

PARP inhibitors in older patients with ovarian and breast cancer: Young International Society of Geriatric Oncology review paper

Breast and ovarian cancer are common malignancies among older adults, causing significant morbidity and mortality. Although most cases of breast and ovarian cancer are sporadic, a significant proportion is caused by mutations in cancer susceptibility genes, most often breast cancer susceptibility genes (BRCA) 1 and 2. Furthermore, some breast and ovarian tumors are phenotypically similar to those with BRCA mutations, a phenomenon known as “BRCAness”. BRCA mutations and “BRCAness” lead to defects in DNA repair, which may be a target for therapeutic agents such as Poly ADP-Ribose Polymerase (PARP) inhibitors. PARP inhibitors are novel medications which lead to double-strand breaks resulting in cell death due to synthetic lethality, and which have been shown to be effective in patients with advanced breast and ovarian cancers with or without BRCA mutations. Three different PARP inhibitors (olaparib, niraparib, and rucaparib) have been approved for the treatment of ovarian cancer and one (olaparib) for breast cancer harboring BRCA mutations. Here, we review the currently available evidence regarding the use of PARP inhibitors for the treatment of patients with breast and ovarian cancer, with a particular focus on the inclusion of older adults in clinical trials of these therapies. Additionally, we provide an overview of currently ongoing studies of PARP inhibitors in breast and ovarian cancer, and include recommendations for increasing the evidence-base for using these medications among older patients.     

中国汉族BRCA1/2突变的乳腺癌家系中其他肿瘤发病风险分析

目的 研究携带BRCA1/2突变的中国汉族家族性乳腺癌家系中非乳腺癌和卵巢癌的其他肿瘤发病风险.方法 采用聚合酶链反应(PCR)-直接测序法检测465个汉族家族性乳腺癌家系中先证者的BRCA1/2基因胚系突变,比较突变组与非突变组有非乳腺癌和卵巢癌的其他肿瘤家族史的比例.结果 在465例汉族家族性乳腺癌先证者中,BRCA1/2突变者47例(10.1％),非突变者418例(89.9％).在BRCA1/2突变组和非突变组中,两者总的非乳腺癌和卵巢癌的其他肿瘤家族史比例差异无统计学意义(突变组与非突变组,27.7％∶29.9％,x2=0.10,P=0.75);但两组的瘤谱分布有差别,在突变组的家族中最常见肿瘤为胃癌、胰腺癌和前列腺癌;而在非突变组家族中最常见的为肺癌、胃癌和食管癌.进一步分析发现胃癌、胰腺癌和前列腺癌3种肿瘤家族史总的比例在突变组中显著高于非突变组(突变组与非突变组,17％∶7.7％,Fisher精确概率法P=0.048).突变组家族中发生胃癌、胰腺癌和前列腺癌的风险为非突变组家族的2.47倍(95％ CI为1.07 ～ 5.74).结论 在中国汉族家族性乳腺癌患者中,相比较于非BRCA1/2突变家系,BRCA1/2突变患者的家系有相对较高的风险发生胃癌、胰腺癌和前列腺癌.     

The BOADICEA model of genetic susceptibility to breast and ovarian cancer

Several genes conferring susceptibility to breast and ovarian cancer, notably BRCA1 and BRCA2, have been identified. The majority of the familial aggregation of breast cancer is, however, not explained by these genes. We have previously derived, using segregation analysis, a susceptibility model (BOADICEA, Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) in which susceptibility to these genes is explained by mutations in BRCA1 and BRCA2 together with a polygenic component reflecting the joint multiplicative effect of multiple genes of small effect on breast cancer risk. Here, we consider the predictions made by this model. The overall familial risks of breast cancer predicted by this model are close to those observed in epidemiological studies. The predicted prevalences of BRCA1 and BRCA2 mutations among unselected cases of breast and ovarian cancer are also consistent with observations from population-based studies. These predictions are closer to the observed values than those obtained using the Claus model and BRCAPRO. The predicted mutation probabilities and cancer risks in individuals with a family history (FH) can differ markedly from those predicted by other models. We conclude that this model provides a rational basis for risk assessment in individuals with a FH of breast or ovarian cancer.     

BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families

Worldwide variation in the distribution of BRCA1 and BRCA2 mutations is well recognised, and for the Belgian population no comprehensive studies about BRCA1/2 mutation spectra or frequencies have been published. We screened the complete coding region of both genes in 451 individuals from 349 Belgian families referred to a family cancer clinic and identified 49 families with a BRCA1 and 26 families with a BRCA2 mutation. Six major recurrent mutations (BRCA1 IVS5+3A>G, 2478-2479insG, E1221X and BRCA2 IVS6+1G>A, 6503-6504delTT, 9132delC) accounted for nearly 60% of all mutations identified. Besides 75 true pathogenic mutations, we identified several variants of unknown clinical significance. In combination with a family history, an early average age of female breast cancer diagnosis (P<0.001), and the presence of a relative with ovarian cancer (P<0.0001) or multiple primary breast cancers (P=0.002), increased the chance for finding a mutation. Male breast cancer was indicative of a BRCA2 mutation segregating in the family (P=0.002). Mutations in the 5'-end of BRCA1 and BRCA2 were associated with a significantly increased risk for ovarian cancer relative to the central portion of the gene. Our study suggests a role for additional breast cancer susceptibility genes in the Belgian population, since mutation detection ratios were low in high-risk breast cancer-only families as compared to breast-ovarian cancer families. Given the large proportion of recurring mutations, molecular testing can now be organised in a more cost-effective way. Our data allow optimisation of genetic counselling and disease prevention in Belgian breast/ovarian cancer families.