遗传性乳腺癌易感基因

遗传性乳腺癌占所有乳腺癌患者的10％～ 25％.遗传因素对部分乳腺癌的发生发展具有重要作用.遗传性乳腺癌的易感基因包括高外显率、中外显率和低外显率易感基因.多种易感基因与遗传性乳腺癌密切相关.     

乳腺癌家系遗传易感基因研究进展

乳腺癌是女性最常见的一种恶性肿瘤,随着细胞生物学和分子生物技术的不断发展,对乳腺癌发病机制的研究也取得了长足进展。家族性乳腺癌与遗传易感基因的突变密切相关,已筛选出3大类乳腺癌遗传相关的高、中、低外显率易感基因,致病基因突变及基因多态性高危位点如何进行鉴定,是对具有遗传倾向性乳腺癌的研究重点,本文将就乳腺癌家系遗传易感基因的研究进展进行综述。      

乳腺癌遗传易感基因的研究进展

乳腺癌是女性中最常见的恶性肿瘤之一。乳腺癌的发生是一个多因素、多步骤的过程,其中遗传因素在乳腺癌的发生和发展中起着重要的作用。目前已经发现一系列乳腺癌遗传易感基因,除了高外显率的BRCA1/2、P53以及HER2基因外,越来越多的中低外显率的易感基因也已经被发现。这些乳腺癌遗传易感基因的发现为乳腺癌预防治疗提供了新的理论指导和思路。     

错配修复基因与肿瘤

错配修复基因是遗传性非息肉性大肠癌（ＨＮＰＣＣ）综合征的遗传易感基因，ＨＮＰＣＣ肿瘤和部分散发性肿瘤的发生相关，该基因突变使细胞的错配修复功能的缺陷，结果出现遗传不稳定，从而易感肿瘤，本文就这方面的研究进行综述。     

乳腺癌易感基因单核苷酸多态性与激素受体状态关联性研究现状

目的回顾和总结国内外关于乳腺癌易感基因的单核苷酸多态性（single nucleotide polymorphism,SNP）与乳腺癌患者体内激素受体（estrogen receptor,ER）状态的关联性研究。方法应用Pubmed和CNKI期刊全文数据库检索系统,以＂乳腺癌、易感基因、单核苷酸多态性（SNP）和激素受体状态＂作为关键词,检索2009-01-2014-05相关文献。纳入标准：1）乳腺癌易感基因位点的相关研究和进展;2）乳腺癌易感基因的SNP和激素受体状态的研究现状和进展;根据纳入标准,符合分析的文献共42篇。结果一些易感基因位点的SNP与激素受体阳性乳腺癌易感性相关,如FGFR2、MP3K1的1p11.2等;而另一些位点如19p13.11和8q24的基因多态性则与激素受体阴性乳腺癌的发病相关;TOX3基因多态性则与激素受体阳性及阴性乳腺癌的发病均相关,且与ER阳性乳腺癌的发病相关性更强。因为乳腺癌的发生和发展是多基因多阶段协同作用的结果,在不同种族、不同地区、不同环境中所开展的研究,不同的SNP位点对乳腺癌的患病风险及激素受体状态的影响不尽相同。结论激素受体状态在乳腺癌的免疫分型中起主要作用,研究乳腺癌易感基因的SNP与激素受体状态的关联性,有助于进一步了解乳腺癌的发病机制、肿瘤转归,有望在关于SNP与乳腺癌分子分型的相关研究上取得新的突破。     

乳腺癌发病的基因调控机制

乳腺癌居女性恶性肿瘤的首位,每年全球约有40万人死于该病,其发病率逐年上升。大量研究表明,易感基因、癌基因、肿瘤抑制基因的异常与乳腺癌的发生、发展密切相关。对乳腺癌发生发展中这些异常基因的认识,是乳腺癌防治的关键。我们对近年来乳腺癌相关基因的最新研究现状进行综述。     

乳腺癌发病的基因调控机制

乳腺癌居女性恶性肿瘤的首位,每年全球约有40万人死于该病,其发病率逐年上升.大量研究表明,易感基因、癌基因、肿瘤抑制基因的异常与乳腺癌的发生、发展密切相关.对乳腺癌发生发展中这些异常基因的认识,是乳腺癌防治的关键.我们对近年来乳腺癌相关基因的最新研究现状进行综述.     

家族性胰腺癌研究进展

家族性胰腺癌是已确定的遗传性肿瘤综合征,为常染色体显性遗传,占全部胰腺癌%左右.随着分子遗传学的发展,研究发现乳腺癌易感基因2、Palladin、周期素依赖激酶抑制因子2A等基因与家族性胰腺癌的发生有关,其中的一些基因突变已被确定为特定的肿瘤综合征的遗传基础.通过对高危人群监测可以在无症状时发现早期胰腺癌或胰腺癌前病变...     

中国遗传性乳腺癌研究经验浅析

遗传性乳腺癌大约占所有乳腺癌的5%～10%,目前的研究显示乳腺癌易感基因（BRCA）1和BRCA2突变能解释很大比例的遗传性乳腺癌,另外还有很多已知基因与遗传性乳腺癌有关,但仍有至少超过50%的遗传性乳腺癌尚无法解释其致病原因。西方国家在20世纪末开始进行BRCAl／2基因突变的研究     

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.     

乳腺癌易感基因研究进展

乳腺癌是可遗传的肿瘤,特别是遗传倾向乳腺癌和遗传背景密切相关；鉴定高外显易感基因的突变或低外显易感基因的多态性位点是目前乳腺癌遗传学研究的热点之一。现就近年来乳腺癌易感基因的遗传学研究及基因变异的筛查技术进展作一综述。     

A novel de novo BRCA1 mutation in a Chinese woman with early onset breast cancer

Germline mutations in the two breast cancer susceptibility genes, BRCA1 and BRCA2 account for a significant portion of hereditary breast/ovarian cancer. De novo mutations such as multiple exon deletion are rarely occurred in BRCA1 and BRCA2. During our mutation screening for BRCA1/2 genes to Chinese women with risk factors for hereditary breast/ovarian cancer, we identified a novel germline mutation, consisting of a deletion from exons 1 to 12 in BRCA1 gene, in a patient diagnosed with early onset triple negative breast cancer with no family history of cancer. None of her parents carried the mutation and molecular analysis showed that this novel de novo germline mutation resulted in down-regulation of BRCA1 gene expression.     

遗传性卵巢癌基因筛查及家族成员管理研究进展

卵巢癌是发生率居于全球女性第三位、死亡率居于首位的妇科恶性肿瘤,其中10%~15%由胚系突变导致,称为遗传性卵巢癌（hereditary ovarian cancer）。遗传性卵巢癌是一种常染色体显性遗传病,它的发生与BRCA1/2等基因突变有关。对家族中的先证者进行基因检测,识别卵巢癌易感基因胚系突变,鉴定遗传性卵巢癌,可以使患者受益于个性化治疗,同时提示家庭成员进行基因筛查,以找出家族中高危致病基因突变的携带者,对携带者实施肿瘤的早期监测和干预。这对于降低疾病发病率和死亡率,改善长期预后有重要临床意义。本文总结现有文献,并就遗传性卵巢癌家族成员基因筛查中的主要基因相关临床意义和管理策略进行综述。     

Clinical management of BRCA1 and BRCA2 mutation carriers

The cancer susceptibility genes BRCA1 and BRCA2 appear to be responsible for virtually all hereditary breast ovarian families, and a smaller subset of hereditary site-specific breast cancer families. Fortunately, effective strategies have been developed to reduce the risk for the development of breast and ovarian cancer in women with BRCA1/2 mutations, making genetic testing for these mutations an important part of the management at women with a strong family history of these diseases. Here, we review the current evidence for risk reduction strategies and outline future research directions.     

The Spectrum of Genetic Mutations in Breast Cancer

Breast cancer is the most common malignancy in women around the world. About one in 12 women in the Westdevelop breast cancer at some point in life. It is estimated that 5%-10% of all breast cancer cases in women arelinked to hereditary susceptibility due to mutations in autosomal dominant genes. The two key players associatedwith high breast cancer risk are mutations in BRCA 1 and BRCA 2. Another highly important mutation canoccur in TP53 resulting in a triple negative breast cancer. However, the great majority of breast cancer casesare not related to a mutated gene of high penetrance, but to genes of low penetrance such as CHEK2, CDH1,NBS1, RAD50, BRIP1 and PALB2, which are frequently mutated in the general population. In this review, wediscuss the entire spectrum of mutations which are associated with breast cancer.     

Heredit?rer Brustkrebs

Breast cancer in women under 40 years old is associated with an elevated risk of cancer also in first degree relatives. The term hereditary breast and ovarian cancer syndrome (HBOC) is derived from the frequent occurrence of both forms of cancer in these families. Approximately 25?C55% of these hereditary cancers can be explained by germline mutations of the susceptibility genes BRCA 1 and BRCA2 and 5?C10% by other syndromes of cancer susceptibility. The remaining diseases are explained by mutations in other genes. BRCA1 and BRCA2 mutations are autosomal dominant with reduced penetrance and coding for tumor suppressor genes. Mutations in these genes often lead to loss of the allele and loss of the second allele leads to loss of function of the corresponding protein and facilitates malignant transformation. Knowledge about genetic reasons has implications for counselling and therapy of individuals seeking advice. Employing individually adjusted measures, early detection can be optimized and the risk of cancer can be decreased. In this article the current data and recommendations with regard to risk of hereditary breast and ovarian cancer are reviewed.     

Methylation profiles of the BRCA1 promoter in hereditary and sporadic breast cancer among Han Chinese

The development of breast cancer is a multistep process associated with complex changes in host gene expression patterns including inactivation of tumor suppressor genes and activation of oncogenes. Critically, hereditary predisposition plays a significant role in cancer susceptibility. However, mutation of the BRCA1 gene is found only in the minority of hereditary breast cancer, which indicates that there might be alternative, novel mechanisms contributing to inactivation of the BRCA1 gene. Studies have shown that aberrant methylation of genomic DNA plays an important role in carcinogenesis. The aim of this study was to investigate whether DNA methylation may be an alternative mechanism for the inactivation of BRCA1 as an epigenetic modification of the genome and whether hereditary breast cancer has a different BRCA1 methylation phenotype pattern than sporadic breast cancer. The pattern of CpG island methylation within the promoter region of BRCA1 was assessed by bisulfite sequencing DNA from peripheral blood cells of 72 patients with hereditary predisposition but without BRCA1 mutations and 30 sporadic breast cancer controls. The overall methylation level in patients with hereditary predisposition was significantly lower than that in the sporadic control group. However, patients with hereditary predisposition showed a significantly higher methylation susceptibility for the sites -518 when compared to controls. These results suggest that there might be different BRCA1 promoter methylation levels and patterns in sporadic and hereditary breast cancer in peripheral blood DNA. These findings may facilitate the early diagnosis of hereditary breast cancer.