江西汉族女性BRCA2基因单核苷酸多态性与散发性乳腺癌易感相关性研究

目的:探讨BRCA2基因单核苷酸多态性(SNP)与江西汉族女性散发性乳腺癌易感性的关系。方法:利用SequenomMassArrayiPLEX GOLD系统对江西南昌大学第一附属医院散发性乳腺癌患者152例和健康对照组165名的BRCA2基因编码区3个单核苷酸多态性位点(rs766173,rs144848,rs1801426)进行基因型检测,非条件Logistic回归分析。结果:rs766173位点基因型和等位基因型频率分布差异均有统计学意义(χ2=4.602,P=0.032;χ2=4.097,P=0.043)。相对TT基因型,TG杂合型与TG+GG型均能显著性增加乳腺癌发生的危险性,OR值(95%CI)分别为1.971(1.060~3.666)和1.934(1.052~3.555),P分别为0.032和0.034。相对等位基因T,等位基因G为易感等位基因,OR值为1.792(95%CI=1.012~3.172,P=0.045)。另外两个位点rs144848和rs1801426多态性分布频率在乳腺癌组和对照组之间差异无统计学意义。结论:rs766173位点基因多态性与江西地区汉族女性散发性乳腺癌易感性相关,另外两个多态性位点rs144848和rs1801426与江西地区女性散发性乳腺癌易感性无关。     

家族性与散发性乳腺癌BRCA1与FANCD2基因相关性的研究

目的:探讨乳腺癌组织BRCA1与FANCD2基因表达,明确BRCA1基因与FANCD2基因之间的相关性.方法:选取104例乳腺癌手术标本,其中家族性乳腺癌52例,散发性乳腺癌52例.采用SP免疫组化法检测BRCA1和FANCD2在家族和散发性乳腺癌组织中的表达.结果:在家族性乳腺癌组织中,BRCA1蛋白阳性表达37例(71.2％),FANCD2蛋白阳性表达18例(34.6％),两组差异有统计学意义,P＜0.05.在散发性乳腺癌组织中,BRCA1蛋白阳性表达19例(36.5％),FANCD2蛋白阳性表达27例(51.9％),两组差异无统计学意义.结论:BRCA1和FANCD2基因表达与乳腺癌的发生和发展存在一定相关性,FANCONI/BRCA 通路的抑制,可能是乳腺癌,尤其是家族性乳腺癌发生发展以及形成的原因之一.     

BRCA1相关A蛋白复合物基因单核苷酸多态性与三阴性乳腺癌易感性研究

背景与目的：BRCA1突变与三阴性乳腺癌发病相关目前已得到学者公认。该研究旨在分析BRCA1相关A蛋白复合物相关基因的单核苷酸多态性(single nucleotide polymorphisms,SNP)与三阴性乳腺癌发病风险的关系,寻找和确定与汉族人群三阴性乳腺癌遗传易感性相关的基因型和单体型。方法：2008年-2011年间414例在复旦大学附属肿瘤医院接受原发性乳腺癌手术的三阴性乳腺癌患者和354例健康妇女进入本病例对照研究。通过对Abraxas、BRE、Rap80、NBA1和BRCC36基因组DNA的37个SNP位点的检测,分析它们与三阴性乳腺癌的相关性。研究者随后检测了652例其他类型乳腺癌和890例健康女性的DNA以证实发现的SNP是否为三阴性特有的遗传相关位点。结果：该研究在第一步研究中发现,NBA1启动子区rs7250266位点突变的G等位基因在三阴性乳腺癌患者中的频率显著低于在正常女性中的频率(0.14 vs 0.19,P<0.01)。对rs7250266位点基因分型显示：与携带CC基因型个体比较,携带GC型个体的三阴性乳腺癌的发病风险显著降低(GC∶OR=0.70,95%CI：0.51~0.97;GG∶OR=0.48,95%CI：0.21~1.07,P=0.03)。单体型分析也证实NBA1基因的不同单体型间三阴性乳腺癌发病风险不同。第二步的研究结果显示,rs7250266位点突变在非三阴性的乳腺癌与正常人群中差异无统计学意义(0.19 vs 0.18,P=0.85)。结论：NBA1基因的rs7250266位点的单核苷酸多态性与汉族女性的三阴性乳腺癌发病风险相关,其突变型等位基因携带者罹患三阴性乳腺癌的风险低于野生型等位基因携带者。     

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。     

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.     

微小RNA加工剪切酶Dicer 1 rs1057035多态性与乳腺癌相关性研究

目的 探讨微小RNA加工剪切酶Dicer 1 rs1057035多态性与中国汉族人群乳腺癌的相关性.方法 收集176例女性乳腺癌患者和216例健康体检女性的外周静脉血,运用二代测序技术分析Dicer 1 rs1057035多态性在乳腺癌患者和健康体检者中的分布频率.结果 Dicer 1 rs1057035基因型分布在女...     

ICAM基因多态性与BRCA1相互作用对乳腺癌危险度的影响

目的:探讨细胞间黏附分子(ICAM)基因座位单核苷酸多态性(SNPs)与乳腺癌危险度之间的关系,以及这些SNPs位点与BRCA1基因相互作用对乳腺癌危险度的影响。方法:研究对象为1034例女性乳腺癌病例和1091例非恶性肿瘤对照。采外周血提DNA后使用基质辅助激光解吸附电离飞行时间质谱检测技术(MALDI-TOF)对SNPs位点进行基因分型。用χ2检验和Logistic回归模型进行统计学分析。结果:rs1056538位点携带C等位基因对个体患乳腺癌具有保护作用(ORCT=0.3423,95%CI:0.2351～0.4982;ORCC=0.5943,95%CI:0.3899～0.9058),而rs2228615AG和rs281439GG基因型个体则有较高的危险度发生乳腺癌(ORrs2228615AG=2.6771,95%CI:1.4938～4.7976;ORrs281439GG=1.9845,95%CI:1.0287～3.8285)。对于携带BRCA1突变的个体,与全部研究对象所得的结果相比,rs1056538位点携带C等位基因的保护作用更为明显(ORCT=0.2797,95%CI:0.1984～0.3321;ORCC=0.4983,95%CI:0.3942～0.7211),rs2228615位点携带G等位基因的危险度更高(ORAG=3.3369,95%CI:1.9195～5.8009;ORGG=2.0289,95%CI:1.1704～3.5170),而rs281439GG基因型危险度改变不大。结论:ICAM基因座位上SNPs与乳腺癌危险度有关。ICAM基因与BRCA1基因间存在相互作用,影响了乳腺癌的危险度。     

BRCA1、BRCA2基因突变与乳腺癌风险预测及治疗

BRCA1/2基因突变与肿瘤的发生关系密切,其机制主要为BRCA1/2蛋白在细胞分裂过程中对染色体结构和基因序列的完整性起到监护作用,从而预防肿瘤的发生。但BRCA1/2基因突变在乳腺癌中的作用机制始终存在争议。探讨BRCA1/2基因的结构与功能、常见突变类型和位点及它们在乳腺癌临床风险预测中的作用,可为临床靶向治疗提供指导。     

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。     

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.     

A Novel Single Nucleotide Polymorphism of the Cyclooxygenase-2 Gene Associated with Breast Cancer

AimsCyclooxygenase-2 (COX-2) is involved in carcinogenesis, immune response suppression, apoptosis inhibition, angiogenesis, and tumour cell invasion and metastasis. The gene for COX-2, designated as PTGS2, carries several polymorphisms, such as ?765G > C, 1195G/A in the promoter region, and 8473T > C in the 3′ UTR, which have been associated with susceptibility to malignant disease. The aim of this study was to search for new mutations and polymorphisms in the COX-2 gene and to assess the relationship with breast cancer.Materials and methodsIn the present study, we identified a novel single nucleotide polymorphism, 169C > G, in exon 2 using polymerase chain reaction–single-strand conformation polymorphism analysis. This nucleotide change causes the amino acid change from proline to alanine at codon 57. To investigate the role of this polymorphism for breast cancer, we determined the prevalence of PTGS2 genotypes in 310 women with breast cancer and 310 gender- and age-matched healthy control subjects.ResultsHomozygous carriers of the 169-GG genotype were more frequent among patients (15.16%) than among controls (9.35%; P = 0.03). The odds ratio for carriers of this genotype for breast cancer was 1.76 (95% confidence interval, 1.20–3.05). Among patients, oestrogen receptor positivity was less frequent among carriers of a GG genotype (61.7%) than among carriers of a CC or GC genotype (72.3%; P = 0.02). Tumour size, histological grade, presence of primary lymph node metastases, progesterone receptor positivity, or age at diagnosis were not associated with PTGS2 genotypes.ConclusionWe conclude that the homozygous PTGS2 169-GG genotype may be associated with breast cancer risk.     

IFN-γ基因+874位点单核苷酸多态性与乳腺癌的相关性

 目的探讨IFN-γ基因+874位点单核苷酸多态性与乳腺癌的相关性。方法采用PCR技术对94例乳腺癌患者及96例正常女性IFN-γ基因+874位点A/T单核苷酸多态性(SNP)进行分析,将PCR产物进行克隆、测序。结果乳腺癌患者IFN-γ基因+874位点TT基因型频率为18.1%,显著高于正常人的8.3%,两者之间比较具有显著性差异(χ²=3.95,P=0.047);乳腺癌病例组T等位基因频率显著高于对照组(χ²=4.984,P=0.026)。进一步分析显示,乳腺癌病例组中不同年龄段基因型频率和等位基因频率相比,均无显著性差异。结论IFN-γ基因+874位点TT基因型可能与乳腺癌的发生相关,T等位基因可能为乳腺癌发生的遗传危险因素。     

肿瘤患者二氢嘧啶脱氢酶基因单核苷酸多态性分析

[目的]检测中国大陆肿瘤患者二氢嘧啶脱氢酶（DPD）基因Exon2、Exon13、Exon14和Exon18的单核苷酸多态性（SNP）类型及其发生频率，观察此SNP是否存在种族差异。[方法]2004年10月～2005年8月随机收集142例患者血标本，其中鼻咽癌患者60例，结直肠癌患者82例。采用PCR技术扩增DPYD基因的Exon2、Exon13、Exon14和Exon18外显子，从正反两个方向对扩增片段进行DNA测序和分析。[结果]在DPYD基因Exon2、Exon13、Exon14、Exon18中发现4种SNP,即T85C（7．04％）、A1627G（20．77％）、T1896C（11．62％）和G2194A（0．70％）。C61T、G62A、A74G、G1601A、T1679G、C1714G和GIVS14＋1ASNP在本研究中未发现。[结论]中国大陆肿瘤患者DPD基因Exon2、Exon13、Exon14、Exon18中存在4种SNP，分别为T185C、A1627G、T1896C和G2194A。     

淋巴细胞弱化因子基因多态性与乳腺癌发病风险研究

目的:探讨B及T淋巴细胞弱化因子(B and T Lymphocyte attenuator,BTLA)SNP位点在黑龙江省妇女乳腺癌患者及正常对照人群中的基因型和等位基因频率;确定BTLA基因与黑龙江省妇女乳腺癌发病风险的相关性.方法:抽取280例乳腺癌患者及262例健康女性外周血5mL,试剂盒提取DNA后.利用聚合酶链式反应限制性片段长度多态性(polymerase chain reaction restriction fragment length polymorphism,PCR-RFLP)技术进行BTLA基因外显子及内含子的SNP位点DNA扩增,检测BTLA基因位点多态性,分析患者与正常对照差别,进而确定该基因与黑龙江省妇女乳腺癌的相关性.结果:乳腺癌患者的BTLA基因外显子及内含子中杂合子基因型高于正常对照者,有统计学差异(P＜0.05,OR>1.00),内含子中rs2705535 GG基因型乳腺癌患者组中的基因频率低于正常对照组(P＜0.05,OR<1.00).A等位基因在乳腺癌患者中频率高于正常对照组(P＜0.05,OR>1.00).具有统计学意义.结论:BT-LA基因多态性与黑龙江省妇女乳腺癌发病风险存在一定关联性.     

Prevalence of BRCA1 and BRCA2 Germline Mutations in Patients of African Descent with Early-Onset and Familial Colombian Breast Cancer

BackgroundPathogenic germline mutations in the BRCA1 and BRCA2 (BRCA1/2) genes contribute to hereditary breast/ovarian cancer (OC) in White/mestizo Colombian women. As there is virtually no genetic data on breast cancer (BC) in Colombians of African descent, we conducted a comprehensive BRCA1/2 mutational analysis of 60 Afro-Colombian families affected by breast/OC.Materials and MethodsMutation screening of the complete BRCA1/2 genes for small-scale mutations and large genomic alterations was performed in these families using next-generation sequencing and multiplex ligation-dependent probe amplification analysis.ResultsFour pathogenic germline mutations, including one novel mutation, were identified, comprising 3 in BRCA1 and one in BRCA2. The prevalence of BRCA1/2 mutations, including one BRCA1 founder mutation (c.5123C>A) previously identified in this sample set, was 3.9% (2/51) in female BC-affected families and 33.3% (3/9) in those affected by both breast and OC. Haplotype analysis of 2 BRCA2_c.2701delC carriers (one Afro-Colombian and one previously identified White/mestizo Colombian patient with BC) suggested that the mutation arose in a common ancestor.ConclusionOur data showed that 2/5 (40%) mutations (including the one previously identified in this sample set) are shared by White/mestizo Colombian and Afro-Colombian populations. This suggests that these 2 populations are closely related. Nevertheless, variations in the BRCA1/2 mutational spectrum among Afro-Colombian subgroups from different regions of the country were observed, suggesting that specific genetic risk assessment strategies need to be developed.     

Distribution of BRCA1 and BRCA2 Mutations in Asian Patients with Breast Cancer

Breast cancer is the most prevalent cancer in Asian females, and the incidence of breast cancer has been increasing in Asia. Because Asian patients develop breast cancer at a younger age than their Caucasian counterparts, the contributions of BRCA1 and BRCA2 (BRCA1/2) mutations in Asians are expected to be different than in Caucasians. The prevalence of BRCA1/2 mutations in the Asian population varies among countries and studies. Most Asian studies have reported more frequent mutations in BRCA2 than in BRCA1, with the exception of studies from India and Pakistan. In addition, the contribution of large genomic rearrangements of BRCA1/2 genes is relatively small in Asian populations in comparison to other ethnic populations. Various statistical models for the prediction of BRCA1/2 mutations have underestimated the risk of having these genetic mutations in Asians, especially in predicting BRCA2 gene mutation. Until recently, BRCA1/2 mutation analyses in Asia were mostly conducted by independent single institutions with different patient selection criteria and using various genotyping methods. However, a couple of Asian groups have initiated nationwide studies collecting BRCA1/2 mutational data. These national collaborative studies will help a comprehensive understanding of the prevalence of BRCA1/2 mutations in the Asian population.     

COX-2基因多态性与非贲门胃癌的发病风险关联

目的 检测COX-2基因单核苷酸多态性(SNP) rs689466、rs5275、rs4648308与非贲门胃癌发病风险的关系.方法 采用TaqMan法对288例非贲门胃癌患者和281例健康对照者所检测的3个SNP进行基因分型;采用Haploview软件构建单体型,并用非条件性Logistic回归计算比值比(OR)及其95％可信区间(CI),以评估各等位基因、基因型及单体型与非贲门胃癌发病风险的关系.结果 rs5275C等位基因和rs4648308A等位基因可增加非贲门胃癌的发病风险;rs5275 CT和CC基因型及rs4648308GA基因型可使非贲门胃癌的发病风险增高(rs5275:CT vs.TT:OR=1.458,95％CI:1.015～2.096;CC vs.TT:OR=3.704,95％CI:1.184～11.59; rs4648308:GA vs.GG:OR=3.387,95％CI:1.953～5.872).单体型分析结果显示:单体型ACA与GTG相比,可增加非贲门胃癌发病风险,OR=3.198,95％CI:1.854～5.516.结论 COX-2基因多态性生rs5275、rs4648308与非贲门胃癌发病风险关联.