家族性乳腺癌的研究现状

乳腺癌是女性最常见的恶性肿瘤之一,家族史是目前流行病学最为肯定的乳腺癌高危因素之一。顾名思义,家族性乳腺癌是指具有家族聚集性的乳腺癌。在一个家族中出现多个乳腺癌患者,这提示我们有两种可能。第一,就是该家族成员携带着某一乳腺癌易感基因;第二种可能是他们共同暴露于     

家族性和早发性乳腺癌BRCA1基因突变分析

目的 分析中国黑龙江省家族性和早发性乳腺癌中BRCA1基因的突变情况。方法 以黑龙江地区的92例家族性和早发性乳腺癌(发病年龄≤35岁)为研究对象。由静脉血提取基因组DNA,对BRCA1基因的全部编码序列(除外1,4号外显子)进行扩增。由聚丙烯酰胺凝胶电泳分析(SSCP)进行突变的初筛,之后进行DNA直接测序证实。结果 在92例乳腺癌患者中发现有5种致病性突变,其中3种为新发现的突变,发现的已报道的2种突变均为无义突变。结论 在中国黑龙江人群中,BRCA1基因的突变对于遗传性乳腺癌的发生可能具有较重要意义;新发现的3个突变位点可能是中国人群中的特有突变;黑龙江地区BRCA1在家族性乳腺癌中突变率明显低于国内外报道,但其中的移码突变3712insG分别在3个患者中检出,提示有可能成为该地区的基础突变。     

家族性乳腺癌—卵巢癌易感基因的研究进展

流行病学研究表明乳腺癌,卵巢癌具有家族聚集性的特点,乳腺癌－卵巢癌易感基因（ＢＲＣＡ１）被定位于色体１７ｑ,从遗传学上证实了这个特点,本文就ＢＲＣＡ１在突变,与肿瘤的相关性,表达产物特点及检测方法等方面的研究进展作一综述。     

中国家族性和早发性乳腺癌BRCA1基因突变的研究

目的　研究中国家族性和早发性乳腺癌患者的BRCA1基因突变情况。方法　选取 4 1例家族性和早发性乳腺癌患者的外周血单个核细胞DNA ,应用PCR SSCP和DNA序列测定方法 ,对BRCA1基因全序列进行突变检测和分析。结果　 4 1例乳腺癌患者中 ,3例发生BRCA1疾病相关性突变 ,其中年龄 <35岁的患者 2例 ,具有乳腺癌家族史的患者 1例。结论　中国早发性乳腺癌患者的BRCA1突变发生率与西方国家相近 ,而家族性乳腺癌患者的突变发生率明显低于西方国家。     

家族性乳腺癌BRCA1/BRCA2基因突变的研究

目的:研究家族性乳腺癌患者BRCA1/ BRCA2基因的突变位点及携带情况.方法:应用聚合酶链反应-单链构象多态性分析(single strand confor- mation polymorphism analysis of polymerase chain reaction products,PCR-SSCP)和基因测序技术,对12个家族性乳腺癌家系的13例患者进行BRCA基因检测.结果:实验发现1个突变位点(4193insA)和2个核苷酸多态性位点(4165T>A,5416C>A).结论:河北地区家族性乳腺癌的BRCA1基因突变率为7.7%,低于国外和国内其它地区;BRCA基因突变携带者家系中成员具有较高的发病风险.     

家族性卵巢癌4例报告并文献复习

大量研究表明,卵巢癌家族史是卵巢癌发病最重要的危险因素。卵巢癌病例呈家族性传递现象[1],即家族性或遗传性卵巢癌综合征(familial or hereditary ovarian cancer syn-drome,FOCS or HOCS)。本文就同一家族亲姐妹4例卵巢癌的临床资料进行分析。     

家族性卵巢癌4例报告并文献复习

大量研究表明,卵巢癌家族史是卵巢癌发病最重要的危险因素。卵巢癌病例呈家族性传递现象[1],即家族性或遗传性卵巢癌综合征（familial or hereditary ovarian cancer syn-drome,FOCS or HOCS）。本文就同一家族亲姐妹4例卵巢癌的临床资料进行分析。     

家族性乳腺癌与散发性乳腺癌的临床生物学特性分析

目的比较家族性乳腺癌与散发性乳腺癌的临床和分子生物学特性，探讨家族性乳腺癌的临床特点和预后。方法回顾性分析河北医科大学第四医院外科2005年6月至2006年5月收治的681例乳腺癌患者的临床资料，其中家族性乳腺癌18例，散发性乳腺癌663例，比较两组间临床生物学行为特点。结果家族性乳腺癌的组织学分级Ⅲ级比例（44．4％）明显高于散发性乳腺癌（17．2％），两组间差异有统计学意义（Х^2=9．943，P=0．007）；家族性乳腺癌的ER阴性率（50．0％）高于散发性乳腺癌（27．0％），两组间差异有统计学意义（Х^2=6．203，P=0．045）；家族性乳腺癌的VEGF表达阳性率（44．4％）高于散发性乳腺癌（21．9％），两组间差异有统计学意义（Х^2=6．783，P=0．034）。但家族性乳腺癌和散发性乳腺癌患者在年龄分布（Х^2=0．505，P=0．918），绝经状况（Х^2=0．915，P=0．633），肿瘤大小（Х^2=1．595，P=0．660），临床分期（Х^2=1．882，P：0．597），病理类型（Х^2=2．430，P=0．876），腋淋巴结转移率（Х^2=0．999，P=0．607），PR（Х^2=3．088，P=0．214）及C—erbB-2表达（Х^2=3．094，P=0．213）等方面的差异均无统计学意义。结论家族性乳腺癌的组织学分级、ER阴性率、VEGF表达阳性率均明显高于散发性乳腺癌，提示预后较差。     

家族性乳腺癌BRCA1／BRCA2基因突变的研究

目的：研究家族性乳腺癌患者BRCAl／BRCA2基因的突变位点及携带情况。方法：应用聚合酶链反应一单链构象多态性分析（singlestrand confor—marion polymorphism analysis of polymerase chain reaetion products,PCR—SSCP）和基因测序技术,对12个家族性乳腺癌家系的13例患者进行BRCA基因检测。结果：实验发现1个突变位点（4193insA）和2个核苷酸多态性位点（4165T〉A,5416C〉A）。结论：河北地区家族性乳腺癌的BRCAl基因突变率为7．7％,低于国外和国内其它地区;BRCA基因突变携带者家系中成员具有较高的发病风险。     

家族性卵巢癌一家系报道

本院在1998年-2005年间收治一家3代6例卵巢癌、乳腺癌及宫颈癌,急性淋巴细胞白血病4种癌症聚集家族,报道如下。 1 临床资料患者(Ⅱ-5),女性,52岁,已婚。于1998年因“痛经32年,加重1年,查见左附件包块”入院。体检时于左附件区扪及直径8cm囊实性包块,欠活动。B超示左附件9．4cm×8cm分割状囊性占位。     

Familial Breast Cancer Risk

The most well recognized breast cancer susceptibility genes are BRCA1 and BRCA2. Studies in individuals carrying mutations in these genes have led to clinical care guidelines for screening and prevention. Beyond BRCA1 and BRCA2, mutations in TP53, PTEN, STK11, and CDH1 also significantly increase the risk of breast cancer. Early identification of women at increased risk of breast cancer due to specific genetic susceptibility may lead to enhanced screening and prevention strategies and potentially improved overall survival for this group of patients as has been seen with carriers of BRCA1 and BRCA2 mutations. In addition to high penetrance genes, increasing numbers of genes that confer a moderate risk of breast cancer have been identified such as CHEK2, PALB2, and ATM; however, the clinical application of these genes is much more challenging. This review will discuss both high and moderate penetrance breast cancer susceptibility genes.     

Four Cases of Familial Breast Cancer

We report 4 families with a remarkable history of cancer, including bilateral breast cancer, early onset breast cancer under age 40, and one or more cancers at other sites. We detected a second malignancy in 4 probands during follow-up after the first operation(families 1, 2, 3 and 4), and could salvage 3 of them (families 2, 3 and 4). We also found 2 family members with cancer by surveillance of family 4 and they underwent suitable treatment (elder sister and elder brother). In conclusion, a knowledge of the natural history of familial breast cancer with particular attention to age at onset and bilaterality may allow for the development of more accurately targeted surveillance, genetic counseling, and management strategies.     

Familial Breast and Bowel Cancer: Does It Exist?

There is much debate in the literature about familial predispositions to breast and bowel cancers yet little evidence is forthcoming to suggest that there are susceptibility genes that can account for such kindreds. Within the context of known susceptibility genes the most controversial syndrome is hereditary non-polyposis colorectal cancer (HNPCC). In HNPCC, breast cancers do occur yet their incidence overall is no different to that of the general population yet when studied at the molecular level these tumours often display DNA microsatellite instability suggesting that they do indeed belong to this genetic entity. In this review we examine the relationship between breast and bowel cancer and suggest a possible explanation for the diverse points of view described in the literature.     

Associations between BRCA Mutations in High-Risk Breast Cancer Patients and Familial Cancers Other than Breast or Ovary

Purpose

We investigated the relationship between BRCA mutations and the distribution of familial cancers other than breast or ovary in high-risk breast cancer patients.

Methods

Patients with breast cancer who had at least one of the following risk factors were enrolled: reported family history of breast or ovarian cancer; 40 years of age or younger age at diagnosis; bilateral breast cancer; or male gender. Genetic testing for BRCA mutation and questionnaires about personal and family histories of malignancies were performed.

Results

Among the 238 eligible patients, 49 (20.6%) patients had BRCA1/2 mutations, which were more frequent in patients with multiple risk factors (p<0.0001). There were 271 members of 156 (65.5%) families who had histories of other primary cancer. The distribution of the families was 119 (63.0%) and 37 (75.5%) in the BRCA-negative and positive group, respectively (p=0.0996). Multiple familial cancers occurred in 70 families, which were significantly more frequent in BRCA-positive families (p=0.0034). By ordinal logistic regression, the occurrence of multiple familial cancers was associated with BRCA mutations (p=0.0045), not with other risk factors. The most common site of disease was the stomach, which is the most common in nationwide. And the proportional incidence of pancreatic cancer (6.8%) was significantly higher than that of nationwide cancer statistics (2.4%, p=0.0137).

Conclusion

BRCA mutations in high-risk breast cancer patients were associated with multiple risk factors and multiple family members with other primary cancers. Genetic counseling based on accurate information should be provided to families with BRCA mutation carriers.     

Familial Pancreatic Cancer

The dismal prognosis of ductal pancreatic adenocarcinoma is mainly attributable to advanced tumor stages at the time of diagnosis. Meanwhile, familial pancreatic cancer is an established hereditary tumor entity that is responsible for approximately 3% of pancreatic cancer (PC) cases. Therefore, analysis of the family history may help to identify individuals at increased risk of developing PC. These include members of families with a history of PC as well as those of families with distinct hereditary cancer syndromes such as Peutz-Jeghers syndrome, hereditary pancreatitis, familial atypical multiple mole melanoma syndrome, hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer. In future, the identification of germline mutations in genes predisposing to PC, together with the analysis of exogenous risk factors, could be used for a more precise risk assessment for the development of PC. This may allow the application of invasive screening methods for the identification of early PC or, even better, its precursor lesions in high-risk individuals, providing the option of timely curative pancreatectomy.     

Estrogen Receptor Beta (ESR2) Polymorphisms in Familial and Sporadic Breast Cancer

Summary Estrogen is involved in both normal mammary development and in breast carcinogenesis. A family history of disease and exposure to estrogen are major risk factors for developing breast cancer. Estrogen exerts its biological effects through binding to the estrogen receptors, estrogen receptor alpha (ESR1) and the more recently discovered estrogen receptor beta (ESR2). Genetic variation in genes involved in estrogen biosynthesis, metabolism and signal transduction have been suggested to play a role in breast cancer risk. We therefore tested the hypothesis that common genetic variants of the ESR2 gene may be associated with increased risk for breast cancer and this risk may vary between breast cancer groups. We investigated three common ESR2 polymorphisms, rs1256049 (G1082A), rs4986938 (G1730A) and rs928554 (Cx+56 A→G) for association to breast cancer risk. A total of 723 breast cancer cases and 480 controls were included in the study. Of the breast cancer cases, 323 were sporadic and 400 were familial, the familial cases were further divided into familial high-risk and familial low-risk breast cancer cases. We found no overall statistically significant association for any of the single polymorphisms studied. Haplotype analysis suggested one haplotype associated with increased risk in sporadic breast cancer patients (OR = 3.0, p = 0.03). Further analysis is needed to elucidate the role of estrogen receptor beta in breast cancer susceptibility.     

丽水市家族性乳腺癌患者BRCA1基因突变分析

摘 要：［目的］ 研究丽水市家族性乳腺癌患者BRCA1基因突变及意义。［方法］ 选取丽水市家族性乳腺癌患者32例,其中5例为双侧乳腺癌,抽取入组患者的外周静脉血,抽提全血基因组DNA,应用 PCR 技术对BRCA1的22个外显子基因序列扩增后直接测序。［结果］ 32例家族性乳腺癌患者中共发现7例BRCA1基因突变,其中2例双侧乳腺癌患者检测出BRCA1基因突变,BRCA1基因突变率为21.86％,8个在BIC数据库中均有报道的突变位点。在第3、11、13号外显子发生3例4个位点同义突变,在第11、16号外显子发生6例4个位点错义突变。突变位点多数位于第11号外显子上,其中有2个同义突变、3个错义突变即2731C>T、3232A>G、3667A>G。［结论］ BRCA1基因突变在丽水市家族性乳腺癌患者中有其自身特点,研究将为丽水市乳腺癌患者的一级和二级预防提供参考依据。