Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial.

CONTEXT: Among cancer-free women aged 35 years or older, tamoxifen reduced the incidence of estrogen receptor (ER)-positive but not ER-negative breast cancer. The effect of tamoxifen on breast cancer incidence among women at extremely high risk due to inherited BRCA1 or BRCA2 mutations is unknown. OBJECTIVE: To evaluate the effect of tamoxifen on incidence of breast cancer among cancer-free women with inherited BRCA1 or BRCA2 mutations. DESIGN, SETTING, AND PARTICIPANTS: Genomic analysis of BRCA1 and BRCA2 for 288 women who developed breast cancer after entry into the randomized, double-blind Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel Project (between April 1, 1992, and September 30, 1999). MAIN OUTCOME MEASURE: Among women with BRCA1 or BRCA2 mutations, incidence of breast cancer among those who were receiving tamoxifen vs incidence of breast cancer among those receiving placebo. RESULTS: Of the 288 breast cancer cases, 19 (6.6%) inherited disease-predisposing BRCA1 or BRCA2 mutations. Of 8 patients with BRCA1 mutations, 5 received tamoxifen and 3 received placebo (risk ratio, 1.67; 95% confidence interval, 0.32-10.70). Of 11 patients with BRCA2 mutations, 3 received tamoxifen and 8 received placebo (risk ratio, 0.38; 95% confidence interval, 0.06-1.56). From 10 studies, including this one, 83% of BRCA1 breast tumors were ER-negative, whereas 76% of BRCA2 breast tumors were ER-positive. CONCLUSION: Tamoxifen reduced breast cancer incidence among healthy BRCA2 carriers by 62%, similar to the reduction in incidence of ER-positive breast cancer among all women in the Breast Cancer Prevention Trial. In contrast, tamoxifen use beginning at age 35 years or older did not reduce breast cancer incidence among healthy women with inherited BRCA1 mutations. Whether tamoxifen use at a younger age would reduce breast cancer incidence among healthy women with BRCA1 mutations remains unknown.     

BRCA1、XRCC1基因多态性与乳腺癌易感性研究进展

乳腺癌易感基因1（BRCA1）是最先被识别的具有遗传倾向的乳腺癌易感基因。X射线交叉互补修复基因1（XRCC1）是一重要的DNA损伤修复基因。BRCA1、XRCC1基因多态性,尤其是其编码区的多态性改变,很可能在乳腺癌发病中起着重要作用。目前研究认为BRCA1、XRCC1多态性对乳腺癌易感性的影响不一,本文在大量阅读最新相关文献基础上集成此综述。     

Management of women with BRCA mutations: a 41-year-old woman with a BRCA mutation and a recent history of breast cancer

Ms E, a 41-year-old BRCA1 mutation carrier, was diagnosed 4 years ago as having breast cancer and opted for breast-conserving therapy. Prior to receiving chemotherapy, she harvested her eggs through in vitro fertilization and subsequently used preimplantation genetic diagnosis; 3 months ago she delivered a healthy boy. This review examines the prevalence of BRCA mutations in women with breast cancer, as well as current recommendations for surgery and systemic therapy in these women. In particular, the risk of a contralateral breast cancer is reviewed to help guide the choice of prophylactic mastectomies vs breast-conserving therapy. The technology of preimplantation genetic diagnosis and genetic testing in relatives of mutation carriers is discussed.     

p53基因多态及单体型分布与乳腺癌危险性的关联研究

目的:探讨p53第72密码子Arg/Pro多态、第3内含子16bp副本和第6内含子G/A多态与乳腺癌的关系。方法:采用以自然人群为基础的病例对照设计,对84例乳腺癌患者和以1∶2频数匹配原则获得的168例对照进行研究,p53基因3种多态的基因分型采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析。单体型分布采用EHlinkage software 1.2分析软件进行估计和比较。结果:乳腺癌患者组和对照组吸烟状况的分布差异有统计学意义,病例组曾经或现在吸烟的个体比例为7.1%,明显高于对照组的1.2%(χ2=6.455,P=0.018),年龄、饮酒状况及一二级亲属家族恶性肿瘤史等基本特征因素分布差异均无统计学意义(P>0.05)。p53的这3种多态基因型在两组间的分布均无统计学意义上的差异(P>0.05)。经上述因素校正后发现,p53的3种基因多态与乳腺癌发病亦没有统计学意义上的关联(P>0.05)。应用EHlinkage software 1.2单体型分析软件显示,上述3种基因多态在对照组内存在连锁不平衡现象,Arg-A-G和Pro-A-G是最常见的2类单体型。单体型组间分布亦不具有显著性差异(P>0.05)。结论:p53基因的上述3种多态与乳腺癌发病风险可能不存在关联,各基因多态存在连锁不平衡现象,Arg-A-G和Pro-A-G是最常见的2类单体型。     

家族性乳腺癌患者115例的BRCA1和BRCA2基因突变检测

目的 研究中国家族性乳腺癌患者中BRCA1/2基因突变的发生率和特性.方法 研究对象为来自全国4个乳腺癌医疗中心的115例家族性乳腺癌患者(包括前期研究的35例),应用DHPLC和DNA序列测定技术对这些患者进行BRCA1/2基因全编码区的突变检测.结果 在115例患者中,共发现11例BRCA1基因突变和3例BRCA2基因突变,总的突变发生率为12.2%.根据家系中乳腺癌患者个数分层后,突变携带率差异无统计学意义.但是携带BRCA1/2基因突变的家系中先证者和所有乳腺癌患者的平均发病年龄显著早于突变阴性的家系(P＜0.01),同时家系中年轻的乳腺癌患者越多,突变携带率就越高.结论 在中国家族性乳腺癌患者中,患者的发病年龄能有效地预测BRCA1/2基因突变的携带率,但是家系中乳腺癌患者个数的预测功能却较差.     

2型糖尿病的遗传和环境病因及其相互关系的流行病学研究

对江苏省１９９７年糖尿病流行病学调查中，筛选出的糖尿病患者１８３例及与其性别、年龄构成相近的正常人对照１６４例，进行了２型糖尿病遗传和环境危险因素的病例对照研究。结果显示：病例组和对照组具有良好的均衡可比性，病例组一级亲属总的累积发病率为３．７６％，与对照组的１．１０％相比，差异有非常显著性（Ｐ＜０．００５）；２型糖尿病的遗传度为３６．２％；Ｌｏｇｉｓｔｉｃ回归分析表明，遗传因素与肥胖、高血压等危险因素共同存在时，糖尿病的发病危险性（ＯＲ）将显著增加，进一步说明２型糖尿病是遗传和环境危险因素共同作用的结果     

Life expectancy gains from cancer prevention strategies for women with breast cancer and BRCA1 or BRCA2 mutations

CONTEXT: Women with BRCA1- or BRCA2-associated breast cancer are at increased risk for contralateral breast cancer and ovarian cancer and therefore may consider secondary cancer prevention strategies, such as prophylactic surgery and tamoxifen therapy. It is not proven to what extent these strategies reduce risk of second cancers in such patients. OBJECTIVE: To examine the effect of tamoxifen therapy, bilateral prophylactic oophorectomy (PO), prophylactic contralateral mastectomy (PCM), and combinations of these strategies on life expectancy for women with unilateral breast cancer and a BRCA1 or BRCA2 gene mutation. DESIGN AND SETTING: Decision analysis using a Markov model. Probabilities for developing contralateral breast cancer and ovarian cancer, dying from these cancers, dying from primary breast cancer, and the reduction in cancer incidence and mortality due to prophylactic surgeries and/or tamoxifen were estimated from published studies. PARTICIPANTS: Hypothetical breast cancer patients with BRCA1 or BRCA2 mutations facing decisions about secondary cancer prevention strategies. INTERVENTIONS: Seven strategies, including 5 years of tamoxifen use, PO, PCM, and combinations of these strategies, compared with careful surveillance. MAIN OUTCOME MEASURES: Total and incremental life expectancy (LE) with each intervention strategy. RESULTS: Depending on the assumed penetrance of the BRCA mutation, compared with surveillance alone, 30-year-old early-stage breast cancer patients with BRCA mutations gain in LE 0.4 to 1.3 years from tamoxifen therapy, 0.2 to 1.8 years from PO, and 0.6 to 2.1 years from PCM. The magnitude of these gains is least for women with low-penetrance mutations (assumed contralateral breast cancer risk of 24% and ovarian cancer risk of 6%) and greatest for those with high-penetrance mutations (assumed contralateral breast cancer risk of 65% and ovarian cancer risk of 40%.) Older age and poorer prognosis from primary breast cancer further attenuate these gains. CONCLUSIONS: Interventions to prevent second cancers, particularly PCM, may offer substantial LE gain for young women with BRCA-associated early-stage breast cancer. Estimates of LE gain may help women and their physicians consider the uncertainties, risks, and advantages of these interventions and lead to more informed choices about cancer prevention strategies.     

XRCC1单核苷酸多态及单体型分布与乳腺癌的相关研究

目的：探讨X线交叉互补基因1（XRCC1）外显子C26304T、G27466A和G28152A三处最常见的单核苷酸多态性（single nucleotide polymorphism，SNP）与乳腺癌的关系。方法：以自然人群为基础的病例对照研究方法，对84例乳腺癌患者组和以1：3成组频数匹配原则获得的252例对照组进行研究，XRCC1 C26304T、G27466A和G28152A SNPs基因分型采用聚合酶链反应-限制性内切酶片段长度多态性（polymerase chain reaction—restriction fragment length polymorphism，PCR—RFLP）分析方法。单体型分布采用EH linkage software 1．2分析软件进行预测和比较。结果：乳腺癌患者组和对照组吸烟状况分布差异有显著性，病例组曾经或现在吸烟个体比例7．1％明显高于对照组2．0％（P〈0．05），性别、年龄、饮酒状况及一二级亲属家族恶性肿瘤史等基本特征因素分布差异均无显著性（P〉0．05）。C26304T、G27466A和G28152A SNPs多态基因型和多态等位基因分布在两组间分布差异均无显著性（P〉0．05）。经上述因素校正后，XRCC1 SNPs与乳腺癌发病没有显著相关关系（P〉0．05）。应用EH linkage software 1．2单体型分析软件显示，XRCC1 SNPs在各组内均存在连锁不平衡现象，CGG、CGA、CAG和TGG是最常见的4类单体型。单体型组间分布同样不存在显著性差异（P〉0．05）。结论：XRCC1 C26304T、G27466A和G28152A SNPs与乳腺癌的风险没有相关关系，各SNPs存在连锁不平衡现象，CGG、CGA、CAG和TGG是最常见的4类单体型。     

郑州地区2型糖尿病患者一级亲属遗传度分析

目的:通过对郑州地区2型糖尿病患者一级亲属患病率和遗传度的分析,探讨遗传因素在2型糖尿病发病中的作用。方法:采用病例对照研究方法,通过随机整群抽样,抽取郑州市3所医院的2型糖尿病患者1256例作为病例组,抽取同期河南省军区医院部分体检健康的人群(1299例)作为对照组。采用非条件Logistic回归分析筛选影响2型糖尿病发病的一级亲属病史,并用Falconer法计算遗传度。结果:病例组一级亲属2型糖尿病患病率为12.1%,高于对照组的5.5%(χ2=101.807,P<0.001),一级亲属遗传度为39.10%。父母亲糖尿病病史(父:OR=1.501,95%CI=1.088～2.071;母:OR=4.095,95%CI=3.120～5.375),兄弟姐妹脑卒中病史(OR=9.860,95%CI=2.933～33.139)、糖尿病病史(OR=7.029,95%CI=3.952～12.504)为危险因素;而父母亲高血压(父:OR=0.494,95%CI=0.386～0.634;母:OR=0.594,95%CI=0.465～0.759)、父母亲高血脂(父:OR=0.395,95%CI=0.228～0.684;母:OR=0.367,95%CI=0.187～0.722)、母亲冠心病(OR=0.495,95%CI=0.319～0.769)、母亲肥胖(OR=0.385,95%CI=0.191～0.773)、兄弟姐妹肥胖(OR=0.423,95%CI=0.183～0.980)为保护因素。结论:遗传因素在2型糖尿病的发生中起重要作用。     

上海地区早发性乳腺癌患者BRCA1和BRCA2基因突变分析

目的研究中国上海地区早发性乳腺癌中BRCA1／BRCA2基因的突变位点及携带情况。方法对象为来自上海地区的50例早发性乳腺癌（发病年龄440岁）,其中13例（26％）有一级亲属患病家族史。由静脉血提取基因组DNA,对BRCA1／2基因的全部编码序列进行扩增。突变分析由变性高效液相色谱分析（DHPLC）进行预筛,之后进行DNA测序证实。结果在BRCA1基因中发现有6个致病突变位点,其中4个为新发现的位点,包括两个移码突变（3449insA,5587-1del8）和两个拼接点突变（IVS17-1G〉T,IVS21＋1G〉C）。BRCA2基因的两个致病突变位点都很接近位于Il号外显子上;其中的1个致病突变位点为移码突变（5950delCT）,另一个错义突变（5911G〉C）可能为新的致病突变位点。另外,共发现有12个新的SNP位点,都未引起氨基酸编码改变;其中,8个在BRCA1基因上,4个在BRCA2基因上。在早发性乳腺癌中,BRCA1基因突变频率（12％）比BRCA2基因（4％）高;BRCA1基因突变频率在有无家族史的患者中分别为30．8％和5．4％。结论新发现的4个BRCA1基因的致病突变位点和一个BRCA2基因的错义突变位点可能是中国人群早发性乳腺癌的特有突变位点;在中国人群中,BRCA1基因突变起着比BRCA2基因更大的作用;本研究为未来的临床基因检测提供了可能的筛查模式。     

乳腺癌易感蛋白1序列结构特征及致病性突变的分析

目的:利用生物信息学方法分析乳腺癌易感基因1(BRCA1)序列结构特征,并预测BRCA1功能编码区突变与致病性遗传效应的关系?方法:采用Maximum Likelihood?ClustalW?SMART和Selecton等在线生物信息学分析工具,对BRCA1进行分子系统发育?保守性?选择压力?结构域?三维结构和错义结构的分析?结果:分析获得195个固定残基位点(10.5%)和393个保守位点(21.1%),其分布是非随机性的;发现人BRCA1序列中的保守结构域BRCT的三维结构与其他物种存在着较大的差异,表明BRCT结构域在不同物种中具有不同的生物学功能;关联性分析证实发生在保守位点的突变致病性高?结论:基于生物信息学的BRCA1序列结构分析,能充分利用相关数据的资源,加深对BRCA1基因变异与肿瘤发生的相关性的认识?     

中国家族性乳腺癌人群中发现重复出现的BRCA1 1100delAT突变

目的观察以前在上海地区家族性乳腺癌人群中发现的BRCA1基因突变是否在扩大的样本中有重复出现。方法对来自国内4个乳腺癌临床研究中心的60个独立的汉族家族性乳腺癌家系进行检测,家系中至少有2个一级亲属或3个二级亲属患原发性乳腺癌。从外周血白细胞中提取基因组DNA,对以前报道过的BRCA1基因致病性突变（1100delAT、WS17-1G〉T、IVS21＋1G〉C和5640delA）应用聚合酶链式反应（PCR）-变性高效液相色谱（DHPLC）分析-DNA直接测序的方法进行特异性分析。选取4个与BRCA1基因连锁的标记（D17S855、D17S1322、D17S1326和D17S1327）进行等位基因型分析。结果在来自中国北方的2个家系中发现有重复出现的BRCA11100delAT突变,并在其中一例的患病亲属中发现携带相同的突变。在检测的片段中还发现了1个新的致病性突变．BRCA15589del8。用与BRCA1基因连锁的标记进行等位基因型分析显示,两个来自中国北方的BRCA1 1100delAT突变携带病例有相同的等位基因型,而与前期研究中发现的上海地区此突变携带者的等位基因型有所差异。BRCA11100delAT突变在所有检测家系中出现的频率为3．16％（3／95）。结论首次在中国大陆家族性乳腺癌人群中发现BRCA1基因有重复出现的突变。BRCA11100delAT突变可能是中国家族性乳腺癌人群中BRCA1基因的突变热点;在中国北方人群中,此突变可能有“始祖效应”,需要在大规模人群中进一步研究证实。     

Variation of breast cancer risk among BRCA1/2 carriers

Context  The risk of breast cancer in BRCA1 and BRCA2 mutation carriers has been examined in many studies, but relatively little attention has been paid to the degree to which the risk may vary among carriers. Objectives  To determine the extent to which risks for BRCA1 and BRCA2 carriers vary with respect to observable and unobservable characteristics. Design, Setting, and Participants  Probands were identified from a population-based, case-control study (Women’s Environmental Cancer and Radiation Epidemiology [WECARE]) of asynchronous contralateral breast cancer conducted during the period of January 2000 to July 2004. Participants previously diagnosed with contralateral breast cancer or unilateral breast cancer were genotyped for mutations in BRCA1 and BRCA2. All participants had their initial breast cancer diagnosed during the period of January 1985 to December 2000, before the age of 55 years. Main Outcome Measure  Incidence of breast cancer in first-degree female relatives of the probands was examined and compared on the basis of proband characteristics and on the basis of variation between families. Results  Among the 1394 participants with unilateral breast cancer, 73 (5.2%) were identified as carriers of deleterious mutations (42 with BRCA1 and 31 with BRCA2). Among the 704 participants with contralateral breast cancer, 108 (15.3%) were identified as carriers of deleterious mutations (67 with BRCA1 and 41 with BRCA2). Among relatives of carriers, risk was significantly associated with younger age at diagnosis in the proband (P = .04), and there was a trend toward higher risk for relatives of contralateral breast cancer vs unilateral breast cancer participants (odds ratio, 1.4 [95% confidence interval, 0.8-2.4]; P = .28). In addition, there were significant differences in risk between carrier families after adjusting for these observed characteristics. Conclusion  There exists broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations.      

STUDY OF BRCAI GENE IN HEREDITARY BREAST AND OVARIAN CANCER

Objective. To investigate the BRCA1 gene in hereditary breast and ovarian cancer, early-onset breast cancer and sporadic ovarian cancer. Methods. The exons of 2, 11 and 20 of BRCA1 gene were analyzed, Polyrnerase chain reaction-single strand conformation analysia(PCR-SSCP) and PCR SSCP combined by restriction enzymes were used to screen for mutations. Mutations were further indentifed by sequencing. The loss of heterozygosity (LOH) were also investigated at the BRCA1 genetic loci D17S855 in 10 hereditary ovarian cancer. Results. A insertion mutation was detected in H7. “C“ was inserted ay nucleotide 797. It would result in truncation of the BRCA1 protein at cndon 277. A missen mutation was detected in an early-onset breast cancer(diagnosed at age 24). At nueleotide position 3732, the substitution of a “G“ to a “C“ in codon 1205 changes a Gly to a Arg. A missen mutation were also detected in three sporadic ovarian cancers. At nu-cleotide position 2051, the substitution of a “T“ to a “G“ in cndon 644 changes a Cys to a Trp. H3 and H7 patients show LOH. Conclusions. BRCA1 gene has an important effect in Chinese hereditary breast and ovarian cancer, its effect on early-onset breast cancer and sporadic ovarian cancer are still to be studied. BRCA1 gene is a tu-mor -suppressor gene.     

Breast and ovarian cancer genetics and prevention

Inherited breast and ovarian cancers account for 10% of all breast and ovarian cancers. Relative to sporadic breast and ovarian cancers, these cancers tend to occur at an earlier age and grow more aggressively. Women with BRCA1 and BRCA2 mutations (BRCA1/2 mutation) have a 65% to 85% cumulative lifetime risk of developing invasive breast cancer and a 15% to 65% cumulative lifetime risk of developing invasive ovarian cancer. Identification of patients with the mutation is therefore crucial, because preventive measures such as prophylactic bilateral mastectomy, prophylactic bilateral salpingpo-oophorectomy and chemoprevention with Tamoxifen can prevent breast and ovarian cancer. Likewise, genetic counseling prior to testing is important, considering the major impact of the test results on an individual's life.     

新疆地区维吾尔族、汉族早发性乳腺癌BRCA1基因突变分析

目的研究新疆地区维、汉两族早发性乳腺癌BRCA1基因突变情况及临床病理特征。方法选取病理确诊的65例（维族35例,汉族30例）早发性乳腺癌标本,运用酶链聚合反应（polymerase chain reaction,PCR）和DNA测序方法检测BRCA1基因突变情况,并结合临床病理因素进行相关分析。结果 65例早发性乳腺癌（发病年龄≤35岁）BRCA1的突变率为21.5%（14/65）,35例维吾尔族早发性乳腺癌BRCA1突变率为34.3%（12/35）,30例汉族早发性乳腺癌BRCA1突变率为6.7%（2/30）。65例早发性乳腺癌BRCA1突变的位点为第2、第10、第18号外显子,共发现14个突变位点,位于Exon10共11个,其中10个可引起氨基酸错义突变,3个无义突变;位于Intron18上的1个拼接点突变。65例早发性乳腺癌中BRCA1基因突变者和未突变者在淋巴结转移状况、P53和Ki-67表达情况、组织学分级方面差异有统计学意义（P〈0.05）。结论疆维地区维族、汉族早发性乳腺癌BRCA1基因突变率差异具有统计学意义（P〈0.05）,突变位点可能是新疆维族早发性乳腺癌的遗传易感性位点,与早发性乳腺癌发病存在关联。BRCA1突变者主要临床表现为淋巴结转移多,P53突变率高、Ki-67蛋白高表达等,提示早发性乳腺癌可能发病早、恶性程度高。     

2型糖尿病发病的遗传因素和环境因素

目的探讨遗传因素与环境因素在2型糖尿病病因组合中的相互关系以及各自所占的比重,为2型糖尿病的综合预防和干预提供科学依据.方法采用l:2配比的病例对照研究和家系调查的方法,选择济宁市新诊断2型糖尿病人56例、医院对照112例,对研究因素进行单因素和多因素条件logistic回归分析并分析遗传方式和遗传率.结果病例组一级亲属总的累积发病率为3.963%,与对照组0.625%相比,差异有非常显著性(P＜0.005);2型糖尿病的遗传度为36.2%;分离分析2型糖尿病符合多基因遗传模式.Logistic回归分析表明肥胖、糖尿病家族史和嗜甜食与2型糖尿病有显著性关系.结论对于该病的防制对策应针对那些有遗传背景的人群,注意避免肥胖,少吃甜食,加强监测,尽早的发现潜在的或亚临床型的2型糖尿病,以便及时治疗,减少糖尿病的危害有着重要意义.     

乳腺癌BRCA1基因突变的研究

目的　乳腺癌易感基因 (BRCA1基因 )是一种抑癌基因。本研究检测BRCA1基因在乳腺癌中的突变情况 ,探讨BRCA1基因突变与乳腺癌的关系。方法　选取 89例乳腺癌患者标本作实验组 ,另取非癌乳腺组织标本 30例作对照组。每一例标本分别捣碎 ,分别用酚 -氯仿抽提法提取DNA ,每例DNA用PCR扩增BRCA1基因的 2、5、1 7、2 0等 4个外显子。分别将每例病人每个外显子的PCR扩增产物进行SSCP分析 ,对出现异常区带的PCR扩增产物进行DNA测序 ,与基因库序列比对分析其突变情况。结果　 30例非癌乳腺组织未检测出BRCA1基因突变 ,89例乳腺癌共检测出 4例突变 ,其中 2例为 5外显子的错义突变 (2 73C >G ,2 87A >T) ,2例为 1 7外显子的错义突变 (5 1 1 5T >C ,5 1 1 6A >G)。乳腺癌BRCA1的基因突变率为 4 5 %(4 / 89)。结论　BRCA1突变与乳腺癌有关系 ,检测BRCA1基因突变对于乳腺癌患病风险评估及早期诊断具有重要意义     

BRCA2在散发性乳腺癌组织中的表达及意义

目的:探讨乳腺癌易感基因2(BRCA2)在散发性乳腺癌组织中的表达及意义,了解BRCA2蛋白的表达与雌激素受体(ER)、孕激素受体(PR)及原癌基因C-erbB-2之间的相关性。方法:采用免疫组化法(SABC)对32例乳腺癌患者癌组织、癌旁组织及正常乳腺组织中BRCA2、C-erbB-2、ER、PR蛋白的表达进行检测并结合年龄、病理组织学分级、腋淋巴结转移情况进行相关性分析。结果:BRCA2在乳腺癌组织中表达的阳性率为56%,而在癌旁及正常乳腺组织中无阳性表达(P<0.05)。BRCA2蛋白的表达在乳腺癌不同组织学分级中有差异(r=0.372 8,P<0.05);与腋下淋巴结转移之间比较差异有显著性(r=0.362 2,P<0.05),但与发病年龄、ER、PR、C-erbB-2表达之间未见相关性。结论:BRCA2蛋白的表达与组织学分级高、腋淋巴结转移相关。BRCA2蛋白的检测有可能成为评估乳腺癌生物学行为和预后的新指标。     

Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer

Context  Given the current context of racial disparities in health and health care and the historical context of eugenics, racial disparities in the use of genetic susceptibility testing have been widely anticipated. However, to our knowledge there are no published studies examining the magnitude and determinants of racial differences in the use of genetic susceptibility testing. Objectives  To investigate the relationship between race and the use of BRCA1/2 counseling among women with a family history of breast or ovarian cancer and to determine the contribution of socioeconomic characteristics, cancer risk perception and worry, attitudes about genetic testing, and interactions with primary care physicians to racial differences in utilization. Design, Setting, and Participants  Case-control study (December 1999-August 2003) of 408 women with a family history of breast or ovarian cancer, of whom 217 underwent genetic counseling for BRCA1/2 testing (cases) and 191 women did not (controls). Participants received primary care within a large health system in greater Philadelphia, Pa. Main Outcome Measures  Probability of carrying a BRCA1/2 mutation, socioeconomic characteristics, perception of breast and ovarian cancer risk, worry about breast and ovarian cancer, attitudes about BRCA1/2 testing, and primary care physician discussion of BRCA1/2 testing were measured prior to undergoing BRCA1/2 counseling for cases and at the time of enrollment for controls. Results  African American women with a family history of breast or ovarian cancer were significantly less likely to undergo genetic counseling for BRCA1/2 testing than were white women with a family history of breast or ovarian cancer (odds ratio, 0.22; 95% confidence interval, 0.12-0.40). This association persisted after adjustment for probability of BRCA1/2 mutation, socioeconomic characteristics, breast and ovarian cancer risk perception and worry, attitudes about the risks and benefits of BRCA1/2 testing, and primary care physician discussion of BRCA1/2 testing (adjusted odds ratio for African American vs white, 0.28; 95% confidence interval, 0.09-0.89). Conclusions  Racial disparities in the use of BRCA1/2 counseling are large and do not appear to be explained by differences in risk factors for carrying a BRCA1/2 mutation, socioeconomic factors, risk perception, attitudes, or primary care physician recommendations. The benefit of predictive genetic testing will not be fully realized unless these disparities can be addressed.