中国汉族女性不同分子分型下的乳腺癌易感位点的关联研究

发布时间：2018-06-18 04:18

本文选题：乳腺癌 + 单核苷酸多态性　；参考：《安徽医科大学》2017年硕士论文

【摘要】：研究背景:乳腺癌是一种源自乳导管内壁或乳腺小叶的癌症,主要临床表现为乳房有肿块、乳头发生凹陷、溢液及糜烂,因晚期容易发生扩散,可能转移至肺、肝等器官,具有很高的致死性。目前,乳腺癌是世界上最常见的女性恶性肿瘤。中国的乳腺癌发病率和死亡率每年都在不断增长,也成为女性患者最常见的恶性肿瘤。乳腺癌可以分为四种亚型:腔上皮A型,腔上皮B型,人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)过表达型,基底样型。不同分子分型下的乳腺癌,其生物学特征,治疗指针以及其预后具有差异。乳腺癌的发病机制十分复杂,遗传因素在其中也发挥着重要的作用。目前通过全基因组关联分析(Genome-Wide Association Studies,GWAS)发现了超过90个乳腺癌的易感区域。其中绝大多数易感基因/区域是在欧洲人群中发现的。然而,只有不到30个区域是在中国汉族人群中被验证出来,因为这两个民族的遗传结构具有差异性,这些易感基因/区域往往在中国女性中表现出弱相关或者不相关。关于中国汉族人群分子分型的研究就更加的少了。本课题组将对四种分子分型进行人群分层结果分析,以期明确在中国汉族人群中不同分型下的乳腺癌的易感基因/区域。研究目的:本研究拟通过对2013年发现的其他人群的乳腺癌易感位点在中国汉族人群分层结果分析,已确定不同分型下的乳腺癌的易感位点。研究方法:本课题组从安徽医科大学第一附属医院和第二附属医院选取了3036例女性乳腺癌患者(其中2935例能匹配上分子分型)与3036例健康对照(女性),所有病例都具有详细的临床数据。本研究通过了安徽医科大学伦理委员会,并严格遵守赫尔辛基宣言。本课题组选取2013年后GWAS报道的欧洲人群发现的32个乳腺癌易感位点,通过Sequmonm Mass Array系统平台对所选的易感位点进行验证实验。所有质控及人群分层等统计学分析是通过SPSS13.0与Plink1.07软件进行分析。研究结果:通过实验研究发现,5q11.2/MAP3K1(rs16886034,rs16886364,rs16886397,rs1017226,rs16886448)和7q32.3/LINC-PINT(rs4593472)与中国汉族腔上皮A型乳腺癌有关,10q26.1/FGFR2(rs35054928)与中国汉族腔上皮B型乳腺癌有关.5q11.2/MAP3K1和7q32.3/LINC-PINT均为第一次证明与中国汉族女性特殊分型下的乳腺癌有关。研究结论:本研究表明不同分子分型下的乳腺癌易感基因/区域并不相同。中国汉族女性乳腺癌特异分子亚型相关位点的研究,有助于更好地了解不同分子亚型的乳腺癌。这些特定的分子亚型相关位点可能对指导临床评估和治疗具有潜在意义。
[Abstract]:Background: breast cancer is a kind of cancer originating from the inner wall of the mammary duct or the lobule of the mammary gland. The main clinical manifestations are breast mass, depression of the nipple, discharge and erosion, and may metastasize to the lung, liver, etc. It is highly lethal. At present, breast cancer is the most common malignant tumor in women in the world. The incidence and mortality of breast cancer in China are increasing every year and become the most common malignant tumor in women. Breast cancer can be classified into four subtypes: type A of luminal epithelium, type B of luminal epithelium, overexpression of human epidermal growth factor receptor 2(human epidermal growth factor receptor 2HER2, and basal type. The biological characteristics, therapeutic pointers and prognosis of breast cancer with different molecular types are different. The pathogenesis of breast cancer is very complex, genetic factors also play an important role in it. At present, Genome-Wide Association Studiesus GWASA has found more than 90 breast cancer susceptible regions. The vast majority of these susceptibility genes / regions were found in European populations. However, less than 30 regions have been verified in Chinese Han population because the genetic structure of the two peoples is different, and these susceptible genes / regions tend to be weakly or uncorrelated in Chinese women. The study on molecular typing of Chinese Han population is even less. In order to identify the susceptible genes / regions of breast cancer in different types of Chinese Han population, we will analyze the stratified results of four molecular genotypes. Objective: this study was designed to determine the susceptibility sites of breast cancer in different types of Chinese Han population by analyzing the results of stratification of breast cancer susceptibility loci found in other populations in 2013. Methods: the study group selected 3036 female breast cancer patients (2935 of whom could match the molecular typing) and 3036 healthy controls (female, all cases) from the first affiliated Hospital and the second affiliated Hospital of Anhui Medical University. All have detailed clinical data. This study adopted the ethics committee of Anhui Medical University and strictly obeyed the Helsinki Declaration. After 2013, 32 breast cancer susceptibility sites were found in European population reported by Gwas. The results were verified by Sequmonm Mass Array system platform. All quality control and population stratification were analyzed by SPSS 13.0 and Plink1.07 software. Results: it was found that 5q11.2 / MAP3K1 rs16886034 rs16886364rs1688886397rs1088226rs16886448) and 7q32.3pLINC-PINT rs4593472) were associated with 10q26.1FGFR2FGFR3505492828) and 5q11.2rMAP3k1 and 7q32.3LINC-PINT related to breast cancer in Chinese Han nationality. Conclusion: different molecular types of breast cancer susceptibility genes / regions are different. The study of specific molecular subtypes of breast cancer in Chinese Han women is helpful to better understand the different molecular subtypes of breast cancer. These specific molecular subtype related loci may be potentially useful in guiding clinical evaluation and treatment.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9

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