本文關(guān)鍵詞：乳腺良性病變癌變風(fēng)險(xiǎn)影響因素的研究　出處：《山東大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 乳腺良性增生性病變 乳腺良性非增生性病變 癌變風(fēng)險(xiǎn) 脂聯(lián)素

【摘要】：研究背景乳腺良性疾病(benign breast disease.BBD)為女性中最常見的乳腺疾病,占女性乳腺疾病的75%以上,其中乳腺良性增生性病變(benign proliferation breast disease,BPBD)在我國(guó)育齡女性中的檢出率為15%-22%,在乳腺�？崎T診中的檢出率高達(dá)50%-70%,其發(fā)病率逐年升高,已成為困擾女性生活及健康的主要疾病。研究發(fā)現(xiàn)乳腺良性疾病與乳腺癌風(fēng)險(xiǎn)高度關(guān)聯(lián),是乳腺癌的危險(xiǎn)因素之一,基于乳腺良性疾病的高發(fā)病率、易復(fù)發(fā)及其癌變可能,人們對(duì)于乳腺良性疾病的重視程度逐年升高。探索BBD與乳腺癌的關(guān)系,可為BBD患者的乳腺癌一級(jí)預(yù)防工作提供策略依據(jù),為探索乳腺癌的發(fā)生發(fā)展奠定理論基礎(chǔ)。乳腺良性疾病是多種乳腺疾病的總稱,按照其癌變風(fēng)險(xiǎn)的高低可分為非增生性病變與增生性病變,后者包括不伴有非典型增生的增生性病變與非典型增生。目前較為一致結(jié)論認(rèn)為,乳腺非增生性病變患者乳腺癌風(fēng)險(xiǎn)與普通人群無(wú)明顯差異,而BPBD患者癌變風(fēng)險(xiǎn)較非增生性病變者顯著升高。探究BPBD患者較乳腺良性非增生性病變患者癌變風(fēng)險(xiǎn)升高的原因,可為BPBD患者的健康指導(dǎo)提供科學(xué)依據(jù),從而延緩甚至阻止BPBD的癌變,為乳腺癌的一級(jí)預(yù)防奠定基礎(chǔ),具有重要臨床意義。影響乳腺癌發(fā)生的因素多種多樣,本課題組前期研究表明,人口學(xué)特征、生活及飲食習(xí)慣、身高體重等人體測(cè)量學(xué)指標(biāo)均與乳腺癌風(fēng)險(xiǎn)存在一定相關(guān)性。同為由正常向癌方向的轉(zhuǎn)變,此類因素町能亦為BPBD較乳腺良性非增生性病變癌變風(fēng)險(xiǎn)升高的原因,故本研究擬針對(duì)此類因素與乳腺良性疾病癌變風(fēng)險(xiǎn)的相關(guān)性進(jìn)行分析。乳腺癌危險(xiǎn)因素可分為乳腺癌家族史、年齡等不可校正因素與飲食、肥胖、吸煙等可校正因素。人們無(wú)法對(duì)前者進(jìn)行干預(yù)更改；而對(duì)于可矯正因素,人們則可根據(jù)意愿對(duì)其進(jìn)行干預(yù)。顯而易見,可校正因素臨床意義更為重大。深入研究BPBD較良性非增生性病變癌變風(fēng)險(xiǎn)升高的可校正因素,尤其是分子水平的可校正因素,可為BPBD患者癌變的預(yù)防提供指導(dǎo)及藥物靶點(diǎn)。肥胖是乳腺癌可校正危險(xiǎn)因素之一,也是乳腺癌眾多影響因素中分子水平研究較為深入的一員,國(guó)內(nèi)外多數(shù)學(xué)者認(rèn)為肥胖可升高乳腺癌風(fēng)險(xiǎn)。肥胖是種系統(tǒng)性炎性疾病,脂肪組織的功能不僅僅為儲(chǔ)存脂肪,也可以通過(guò)內(nèi)分泌、旁分泌等方式分泌許多種脂肪因子,脂肪因子被認(rèn)為是肥胖和乳腺癌兩者之間分子水平的紐帶。在眾多脂肪因子中,脂聯(lián)素是唯一一種隨肥胖程度增加而血漿水平降低的脂肪因子。越來(lái)越多的研究結(jié)果顯示,脂聯(lián)素可能是肥胖致癌的關(guān)鍵因素之一,與乳腺癌發(fā)病風(fēng)險(xiǎn)間存在一定關(guān)系,在乳腺癌的發(fā)生過(guò)程中發(fā)揮重要作用。本課題組前期研究亦表明,在絕經(jīng)后女性的亞組中,脂聯(lián)素是乳腺癌的保護(hù)因素。鑒于脂聯(lián)素在乳腺癌發(fā)病中發(fā)揮的作用,我們推測(cè)其可能為BPBD較非增生性病變癌變風(fēng)險(xiǎn)高的分子水平原因。人體血漿中脂聯(lián)素由高、中、低分子量脂聯(lián)素等不同組分構(gòu)成,各組分在生物學(xué)活性、對(duì)不同受體的親和力等方面各不相同,而高分子量脂聯(lián)素(high molecular weight adiponectin,HMWAPN)在2型糖尿病、炎癥、代謝綜合征、心臟病、惡性腫瘤等方面的研究中均具有一定的特殊性。本課題組通過(guò)1167對(duì)乳腺癌病例-對(duì)照研究發(fā)現(xiàn),血漿總脂聯(lián)素水平與乳腺癌風(fēng)險(xiǎn)無(wú)關(guān),而血漿HMW脂聯(lián)素水平與乳腺癌患病風(fēng)險(xiǎn)呈負(fù)相關(guān)。這說(shuō)明脂聯(lián)素不同組分對(duì)于乳腺組織的作用存在差異,HMW脂聯(lián)素可能在其中發(fā)揮更重要的作用。故將脂聯(lián)素各組分區(qū)分開,研究血漿總脂聯(lián)素、血漿脂聯(lián)素主要活性形式HMW脂聯(lián)素以及脂聯(lián)素分子構(gòu)成(HMW脂聯(lián)素／總脂聯(lián)素比值)而非僅研究總脂聯(lián)素與乳腺良性疾病癌變風(fēng)險(xiǎn)的關(guān)系十分必要。綜上,本研究旨在探索人口學(xué)特征、生活及飲食習(xí)慣、身高體重等環(huán)境危險(xiǎn)因素以及血漿HMW脂聯(lián)素、總脂聯(lián)素、HMW/總脂聯(lián)素比值等分子水平因素是否為乳腺良性增生性病變較乳腺良性非增生性病變癌變風(fēng)險(xiǎn)高的原因,進(jìn)而為乳腺癌的一級(jí)預(yù)防提供策略指導(dǎo)。研究目的1、探討環(huán)境因素是否為乳腺良性增生性病變較非增生性病變癌變風(fēng)險(xiǎn)高的原因,分析各因素間的交互作用,為乳腺良性增生性病變癌變的預(yù)防提供理論支持。2、探索血漿總脂聯(lián)素、HMW脂聯(lián)素、HMW/總脂聯(lián)素比值在BPBD組與乳腺良性非增生性病變組間水平的差異,探討其是否為BPBD患者癌變風(fēng)險(xiǎn)高的原因,為BPBD癌變的預(yù)防提供分子靶點(diǎn)。研究方法1、病例對(duì)照研究采用11個(gè)省23家研究中心參加的以醫(yī)院為基礎(chǔ)的病例對(duì)照研究,以23家三級(jí)甲等醫(yī)院住院治療的女性為研究對(duì)象,按照病理結(jié)果劃分乳腺良性非增生性病變組與乳腺良性增生性病變組,采用面對(duì)面訪談形式填寫調(diào)查問(wèn)卷,于病歷中獲得其B超、鉬靶、病理等數(shù)據(jù)資料。2、酶聯(lián)免疫吸附法(ELISA)檢測(cè)血漿總脂聯(lián)素、HMW脂聯(lián)素水平采用人外周血總脂聯(lián)素、HMW脂聯(lián)素檢測(cè)試劑盒對(duì)兩組研究對(duì)象血漿中總脂聯(lián)素、HMW脂聯(lián)素水平進(jìn)行檢測(cè)。3、統(tǒng)計(jì)學(xué)分析方法本研究應(yīng)用的統(tǒng)計(jì)學(xué)分析軟件為SPSS22.0。采用配對(duì)t檢驗(yàn)描述連續(xù)性數(shù)值變量,以均數(shù)士標(biāo)準(zhǔn)差(Mean±SD)、t值表示；采用Chi-square檢驗(yàn)對(duì)分類變量進(jìn)行描述,以n(%)、χ2表示。在a=0.05的水平上,使用非條件單因素Logistic回歸分析將各因素及脂聯(lián)素各組分與不同乳腺良性病變之間癌變風(fēng)險(xiǎn)差異的關(guān)系,對(duì)單因素Logistic回歸分析后具有統(tǒng)計(jì)學(xué)意義的因素進(jìn)行多因素Logistic回歸分析,并對(duì)多因素分析后有統(tǒng)計(jì)學(xué)意義的各因素進(jìn)行交互作用分析。研究結(jié)果1、研究對(duì)象的基本特征BPBD組共416例,平均年齡為45.58±7.62歲；乳腺良性非增生性病變組共166例,平均年齡為44.25±9.32歲。2、乳腺良性病變癌變風(fēng)險(xiǎn)相關(guān)的因素分析取a=0.05,單因素Logistic!回歸分析發(fā)現(xiàn),中心性肥胖(以腰臀比≥0.85)為乳腺良性疾病患者癌變的危險(xiǎn)因素,經(jīng)常飲茶、HMW/總脂聯(lián)素比值升高為保護(hù)性因素,多因素分析后進(jìn)一步證實(shí),中心性肥胖(以腰臀比≥0.85為標(biāo)準(zhǔn))(P=0.041,OR=12.566,95%CI,：1.105-142.861)為獨(dú)立于飲茶等因素的危險(xiǎn)因素,HMW/總脂聯(lián)素比值升高(P=0.038,OR=0.629,95%CI：0.407-0.975)為獨(dú)立的保護(hù)性因素。3、交互作用分析�。�=0.05,中心性肥胖(腰臀比≥0.85)與飲茶間存在正交互作用(P=0.020,OR=1.227,95%CI：1.032-1.458),即在中心性肥胖的女性中,若不經(jīng)常飲茶,若患者為乳腺良性增生性病變,則其癌變風(fēng)險(xiǎn)將增加。結(jié)論1、中心性肥胖(腰臀比≥0.85)、不經(jīng)常飲茶為乳腺良性增生性病變較乳腺良性非增生性病變癌變風(fēng)險(xiǎn)高的原因之一。2、血漿中不同形式的脂聯(lián)素組分對(duì)于乳腺良性疾病癌變風(fēng)險(xiǎn)的影響不同,血漿HMW脂聯(lián)素、總脂聯(lián)素水平與乳腺良性疾病癌變風(fēng)險(xiǎn)的差異無(wú)關(guān)；血漿HMW脂聯(lián)素／總脂聯(lián)素比值高是乳腺良性非增生性病變較乳腺良性增生性病變癌變風(fēng)險(xiǎn)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.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R737.9

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