乳腺良性病变癌变风险影响因素的研究

发布时间：2018-01-13 11:31

本文关键词：乳腺良性病变癌变风险影响因素的研究　出处：《山东大学》2016年硕士论文　论文类型：学位论文

【摘要】：研究背景乳腺良性疾病(benign breast disease.BBD)为女性中最常见的乳腺疾病,占女性乳腺疾病的75%以上,其中乳腺良性增生性病变(benign proliferation breast disease,BPBD)在我国育龄女性中的检出率为15%-22%,在乳腺专科门诊中的检出率高达50%-70%,其发病率逐年升高,已成为困扰女性生活及健康的主要疾病。研究发现乳腺良性疾病与乳腺癌风险高度关联,是乳腺癌的危险因素之一,基于乳腺良性疾病的高发病率、易复发及其癌变可能,人们对于乳腺良性疾病的重视程度逐年升高。探索BBD与乳腺癌的关系,可为BBD患者的乳腺癌一级预防工作提供策略依据,为探索乳腺癌的发生发展奠定理论基础。乳腺良性疾病是多种乳腺疾病的总称,按照其癌变风险的高低可分为非增生性病变与增生性病变,后者包括不伴有非典型增生的增生性病变与非典型增生。目前较为一致结论认为,乳腺非增生性病变患者乳腺癌风险与普通人群无明显差异,而BPBD患者癌变风险较非增生性病变者显著升高。探究BPBD患者较乳腺良性非增生性病变患者癌变风险升高的原因,可为BPBD患者的健康指导提供科学依据,从而延缓甚至阻止BPBD的癌变,为乳腺癌的一级预防奠定基础,具有重要临床意义。影响乳腺癌发生的因素多种多样,本课题组前期研究表明,人口学特征、生活及饮食习惯、身高体重等人体测量学指标均与乳腺癌风险存在一定相关性。同为由正常向癌方向的转变,此类因素町能亦为BPBD较乳腺良性非增生性病变癌变风险升高的原因,故本研究拟针对此类因素与乳腺良性疾病癌变风险的相关性进行分析。乳腺癌危险因素可分为乳腺癌家族史、年龄等不可校正因素与饮食、肥胖、吸烟等可校正因素。人们无法对前者进行干预更改；而对于可矫正因素,人们则可根据意愿对其进行干预。显而易见,可校正因素临床意义更为重大。深入研究BPBD较良性非增生性病变癌变风险升高的可校正因素,尤其是分子水平的可校正因素,可为BPBD患者癌变的预防提供指导及药物靶点。肥胖是乳腺癌可校正危险因素之一,也是乳腺癌众多影响因素中分子水平研究较为深入的一员,国内外多数学者认为肥胖可升高乳腺癌风险。肥胖是种系统性炎性疾病,脂肪组织的功能不仅仅为储存脂肪,也可以通过内分泌、旁分泌等方式分泌许多种脂肪因子,脂肪因子被认为是肥胖和乳腺癌两者之间分子水平的纽带。在众多脂肪因子中,脂联素是唯一一种随肥胖程度增加而血浆水平降低的脂肪因子。越来越多的研究结果显示,脂联素可能是肥胖致癌的关键因素之一,与乳腺癌发病风险间存在一定关系,在乳腺癌的发生过程中发挥重要作用。本课题组前期研究亦表明,在绝经后女性的亚组中,脂联素是乳腺癌的保护因素。鉴于脂联素在乳腺癌发病中发挥的作用,我们推测其可能为BPBD较非增生性病变癌变风险高的分子水平原因。人体血浆中脂联素由高、中、低分子量脂联素等不同组分构成,各组分在生物学活性、对不同受体的亲和力等方面各不相同,而高分子量脂联素(high molecular weight adiponectin,HMWAPN)在2型糖尿病、炎症、代谢综合征、心脏病、恶性肿瘤等方面的研究中均具有一定的特殊性。本课题组通过1167对乳腺癌病例-对照研究发现,血浆总脂联素水平与乳腺癌风险无关,而血浆HMW脂联素水平与乳腺癌患病风险呈负相关。这说明脂联素不同组分对于乳腺组织的作用存在差异,HMW脂联素可能在其中发挥更重要的作用。故将脂联素各组分区分开,研究血浆总脂联素、血浆脂联素主要活性形式HMW脂联素以及脂联素分子构成(HMW脂联素／总脂联素比值)而非仅研究总脂联素与乳腺良性疾病癌变风险的关系十分必要。综上,本研究旨在探索人口学特征、生活及饮食习惯、身高体重等环境危险因素以及血浆HMW脂联素、总脂联素、HMW/总脂联素比值等分子水平因素是否为乳腺良性增生性病变较乳腺良性非增生性病变癌变风险高的原因,进而为乳腺癌的一级预防提供策略指导。研究目的1、探讨环境因素是否为乳腺良性增生性病变较非增生性病变癌变风险高的原因,分析各因素间的交互作用,为乳腺良性增生性病变癌变的预防提供理论支持。2、探索血浆总脂联素、HMW脂联素、HMW/总脂联素比值在BPBD组与乳腺良性非增生性病变组间水平的差异,探讨其是否为BPBD患者癌变风险高的原因,为BPBD癌变的预防提供分子靶点。研究方法1、病例对照研究采用11个省23家研究中心参加的以医院为基础的病例对照研究,以23家三级甲等医院住院治疗的女性为研究对象,按照病理结果划分乳腺良性非增生性病变组与乳腺良性增生性病变组,采用面对面访谈形式填写调查问卷,于病历中获得其B超、钼靶、病理等数据资料。2、酶联免疫吸附法(ELISA)检测血浆总脂联素、HMW脂联素水平采用人外周血总脂联素、HMW脂联素检测试剂盒对两组研究对象血浆中总脂联素、HMW脂联素水平进行检测。3、统计学分析方法本研究应用的统计学分析软件为SPSS22.0。采用配对t检验描述连续性数值变量,以均数士标准差(Mean±SD)、t值表示；采用Chi-square检验对分类变量进行描述,以n(%)、χ2表示。在a=0.05的水平上,使用非条件单因素Logistic回归分析将各因素及脂联素各组分与不同乳腺良性病变之间癌变风险差异的关系,对单因素Logistic回归分析后具有统计学意义的因素进行多因素Logistic回归分析,并对多因素分析后有统计学意义的各因素进行交互作用分析。研究结果1、研究对象的基本特征BPBD组共416例,平均年龄为45.58±7.62岁；乳腺良性非增生性病变组共166例,平均年龄为44.25±9.32岁。2、乳腺良性病变癌变风险相关的因素分析取a=0.05,单因素Logistic!回归分析发现,中心性肥胖(以腰臀比≥0.85)为乳腺良性疾病患者癌变的危险因素,经常饮茶、HMW/总脂联素比值升高为保护性因素,多因素分析后进一步证实,中心性肥胖(以腰臀比≥0.85为标准)(P=0.041,OR=12.566,95%CI,：1.105-142.861)为独立于饮茶等因素的危险因素,HMW/总脂联素比值升高(P=0.038,OR=0.629,95%CI：0.407-0.975)为独立的保护性因素。3、交互作用分析取ａ=0.05,中心性肥胖(腰臀比≥0.85)与饮茶间存在正交互作用(P=0.020,OR=1.227,95%CI：1.032-1.458),即在中心性肥胖的女性中,若不经常饮茶,若患者为乳腺良性增生性病变,则其癌变风险将增加。结论1、中心性肥胖(腰臀比≥0.85)、不经常饮茶为乳腺良性增生性病变较乳腺良性非增生性病变癌变风险高的原因之一。2、血浆中不同形式的脂联素组分对于乳腺良性疾病癌变风险的影响不同,血浆HMW脂联素、总脂联素水平与乳腺良性疾病癌变风险的差异无关；血浆HMW脂联素／总脂联素比值高是乳腺良性非增生性病变较乳腺良性增生性病变癌变风险低的分子水平原因之一。
[Abstract]:The research background of benign breast disease (benign breast disease.BBD) is the most common breast disease in women, accounting for more than 75% female breast diseases, including breast benign hyperplasia (benign proliferation breast disease, BPBD) were detected in women of childbearing age in China was 15%-22%, the breast clinic detection rate as high as 50%-70%, the incidence rate increased year by year, has become the lives of women and health. The study found that the main disease of benign breast disease and breast cancer risk associated with height, is one of the risk factors of breast cancer, benign breast disease of high incidence rate based on recurrence and canceration, increasing the degree of importance for the people of benign breast disease. To explore the relationship between BBD and breast cancer, can provide the basis for the strategy of primary prevention of BBD in patients with breast cancer, the theoretical foundation for exploring the development of breast cancer. Breast Benign breast disease is a general term for a variety of diseases, according to the cancer risk can be divided into non proliferative lesions and hyperplastic lesions, the latter includes not accompanied by an atypical hyperplasia and atypical hyperplasia. A more consistent conclusion that non breast hyperplasia disease risk of breast cancer patients and the general population had no significant difference. BPBD patients with cancer risk compared with non proliferative lesions were significantly increased. BPBD on patients than in benign breast hyperplasia of the non reason of increased risk of cancer, can provide scientific basis for health education of patients with BPBD, so as to delay or even prevent the canceration of BPBD, lay the foundation for the primary prevention of breast cancer has important clinical significance. A variety of factors. The occurrence of breast cancer is diverse, previous researches have shown that demographic characteristics, lifestyle and diet, body weight and height measurement index There are certain correlation with the risk of breast cancer. With normal to the direction of change on the grounds of cancer, such as CHO can also BPBD than non benign proliferative lesions cause of elevated cancer risk, so this study aimed at this kind of correlation factors and benign disease of breast cancer risk were analyzed. The risk factors of breast cancer can be divided into a family history of breast cancer, age and other factors and can't be corrected diet, obesity, smoking and other factors can be corrected. People unable to intervene to change the former; and for correction factors, people can intervene in accordance with its wishes. Obviously, correction factors were more significant clinical significance. Further research is BPBD benign non correctable factors increase the risk of cancer lesions, especially the correction factors at the molecular level, the prevention for BPBD cancer patients to provide guidance and drug targets. Obesity is breast cancer can be corrected The risk factors of breast cancer, but also many factors affect a more in-depth study of the molecular level members at home and abroad, many researchers believe that obesity can increase the risk of breast cancer. Obesity is a systemic inflammatory disease, adipose tissue function not only for the storage of fat, also can through endocrine, paracrine secretion of many kinds of way fat factor, fat factor is considered to be the link between obesity and breast cancer in both molecular level. In many adipokines, adiponectin is the only one with the severity of obesity and increased plasma levels of reduced fat factor. More and more studies showed that adiponectin may be one of the key factors causing obesity, there is a certain relationship with the disease the risk of breast cancer, play an important role in carcinogenesis of breast cancer. Our previous studies also showed that women in the postmenopausal subgroup, adiponectin is milk The protective factors of adenocarcinoma. In view of adiponectin in the pathogenesis of breast cancer play a role, we conclude that the BPBD may be compared with non proliferative and malignant lesions of high risk. The molecular level of adiponectin in human plasma by high, in different groups of low molecular weight adiponectin and other components, each component in the biological activity of different receptors the affinity of different and high molecular weight adiponectin (high molecular weight adiponectin, HMWAPN) inflammation in type 2 diabetes, metabolic syndrome, heart disease, the particularity of cancer research in other aspects. The research group through the control study found that 1167 of breast cancer cases, plasma total adiponectin has nothing to do with the risk of breast cancer, and HMW of plasma adiponectin levels and breast cancer risk was negatively correlated. This shows that the different groups for the role of adiponectin in breast tissue differences, adiponectin HMW May play a more important role. It will separate the research groups of adiponectin, plasma total adiponectin, the main active form of plasma adiponectin and adiponectin adiponectin HMW molecules (HMW adiponectin / total adiponectin ratio) rather than a relationship only of total adiponectin and breast cancer risk of disease is very necessary. In conclusion, this study aims to explore the demographic characteristics, lifestyle and diet, weight and height of environmental risk factors and plasma adiponectin HMW, total adiponectin, adiponectin ratio of total factor HMW/ molecular level whether benign proliferative lesions of the breast with breast benign non causes high risk hyperplasia canceration, so as to provide strategic guidance for primary prevention of breast cancer. The purpose of the study 1, to investigate whether environmental factors for breast benign proliferative lesions than in the non reason of high risk hyperplasia canceration, analysis among various factors The interaction of.2, to provide theoretical support for the prevention of benign proliferative lesions of the breast cancer, explore the plasma total adiponectin, adiponectin, HMW, HMW/ between the total adiponectin ratio in BPBD group and non proliferative benign breast lesion group level, to explore the reasons for whether the high risk patients with BPBD cancer, provide molecular targets for the prevention of cancer BPBD the. 1 research methods, comparative study of case-control study with 11 provinces and 23 research centers in the hospital-based case, with 23 three level of first-class hospital treatment of women as the research object, according to the pathological results into non benign breast hyperplasia and breast benign hyperplasia by group. Face-to-face interviews questionnaires to record the ultrasound, mammography, pathology data.2, enzyme-linked immunosorbent assay (ELISA) detection of plasma total adiponectin and adiponectin levels by HMW The total peripheral blood adiponectin, adiponectin HMW kit for the detection of total adiponectin in two groups of subjects were detected.3 HMW in plasma adiponectin levels, statistical analysis statistical analysis software used in this study was SPSS22.0. by paired t test description of continuous numerical variables as mean SD (Mean + SD), t value Express; Chi-square test was used for description of the classification variables, n (%), was 2. At the level of a=0.05, the regression analysis of the various factors and adiponectin components between cancer risk among different breast benign lesions using a single factor non conditional Logistic, the single factor Logistic regression analysis with the statistical significance of the multivariate Logistic regression analysis, and the factors in multivariate analysis after statistically significant interaction analysis. Results: 1, study the basic characteristics of the BPBD group of 4 In 16 cases, the average age was 45.58 + 7.62; non benign breast hyperplasia lesions were 166 cases, the average age was 44.25 + 9.32.2, benign lesions of breast cancer risk factors related to a=0.05 analysis, single factor regression analysis showed that Logistic! (central obesity with waist to hip ratio greater than or equal to 0.85) for danger cancer patients with benign breast disease, often tea increased HMW/ total adiponectin ratio as a protective factor, multivariate analysis further confirmed that the central obesity (waist to hip ratio greater than 0.85 for the standard (P=0.041), OR=12.566,95%CI,:1.105-142.861) as the independent risk factors of tea and other factors, the total adiponectin ratio increased (HMW/ P=0.038, OR=0.629,95%CI:0.407-0.975) were the protective factors of independent.3, the interaction analysis of a=0.05, central obesity (waist to hip ratio greater than or equal to 0.85) there is a positive interaction between tea and (P= 0.020, OR=1.227,95%CI:1.032-1.458 That is,) in women with central obesity, if not often drink tea, if patients with benign proliferative lesions of the breast, the risk of cancer will increase. Conclusion 1, central obesity (waist to hip ratio greater than or equal to 0.85), not often tea for breast benign hyperplasia of breast benign proliferative lesions than non cancer risk one of the reasons of high.2, plasma adiponectin in groups of different effects for benign disease of breast cancer risk of HMW plasma adiponectin, regardless of differences in total adiponectin levels and breast cancer risk of benign disease; plasma adiponectin HMW / total adiponectin ratio value is higher in benign breast lesions than non proliferative breast molecular level of risk low benign hyperplasia of canceration.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R737.9

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