published_or_final_version / Nursing Studies / Master / Master of Nursing in Advanced Practice

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Breast cancer is the most common cancer in women in most part of the world. Although there are multiple risk factors which have been reported to be related to breast factors, by far one of the highest risk of breast cancer is the inheritance of the BRCA1 and BRCA2 cancer susceptibility genes. The lifetime risk of breast cancer can be as high as 60-80% for BRCA mutation carriers. As the breast cancer epidemiology and genetic predisposition is increasingly understood, it transpires that ethnic differences exist. Although variations of genetic factors may play a role, the reasons for these differences remain unclear. Most published data are Caucasian based and there are limited publications on hereditary breast cancer in Asians available to date. This thesis hypothesizes that due to the known differences in genetic predisposition in different ethnic groups, it is likely that the mutation spectrum of BRCA mutations and breast cancer characteristics of Hong Kong Chinese, a relatively unexplored cohort, will differ to that of Caucasians. Moreover, the ancestors of local Hong Kong population migrated from Mainland China of which majority were from Southern China. They then remained in Hong Kong and populated and hence similar to smaller countries such as Iceland and Poland where founder mutations are identified, it is likely that a founder mutation will be present. Lastly due to different cultural differences and availability of screening facilities, management options of those found to carry the BRCA mutation may differ to that of other countries. The aims of this study are as follows 1) Perform a comprehensive genetic and phenotypic analysis using Full Gene Sequencing and Multiplex ligation-dependent probe amplification (MLPA) testing of Hong Kong Chinese cohort or breast cancer patients/families who are clinically high risk and to develop a registry to collect data related to this study. 2) To identify the spectrum of BRCA mutation in Hong Kong. 3) To report, any novel mutations, founder mutations, large rearrangements and deletions (using MLPA) if any are found. 4) If founder mutations are present, to develop a fasting and cheaper technique so that rapid screening can be offered. 5) To identify the choice of management in this high risk cohort. A total of 451 clinically high-risk breast and /or ovarian cancer patients from 1 March 2007 to 28 February 2011 were recruited. Based on sequencing results, 59 (13.1%) deleterious BRCA gene mutations were identified: 24 (41%) were in BRCA1 and 35 (59%) in BRCA2. Of the 59 deleterious mutations, 22 (37%) were novel mutations, 8 were BRCA1 and 14 were BRCA2 mutations. Eight recurrent mutations were identified of which four were proven to be founder mutations. These results showed that both BRCA1 and BRCA2 mutations account for a substantial proportion of hereditary breast/ovarian cancer in Sothern Chinese population. By using MLPA, four patients with large genomic rearrangement were identified and one of whom has a de novo BRCA1 mutation encompassing exons 1 to 12 deletion. Such mutations are rare and this de novo mutation has not been previously reported. Moreover another novel BRCA2 variant of unknown significance (c.7806-9T>G), a splice-site intronic mutation, was recharacterized to be pathogenic due to clinical suspicion based on its co-segregation. High Resolution Melting Technique in performing rapid screening for the founder mutations was developed and tested on a further cohort confirming the possibility of the use of founder mutations screening technique in future. Finally, concerning the management choice of BRCA mutation carriers undertaken in Chinese, BRCA mutation carriers in our cohort are more likely to choose intensive surveillance as an option of risk management rather than prophylactic interventions. In summary, this study provides valuable information on mutation spectrum of BRCA1 and BRCA2 in Southern Chinese population. Identifications founder mutations and knowledge of its prevalence in this Chinese population provides important information both to genetic counselling and risk assessment as well as to development of a cost-effective screening strategy. Furthermore, our study on the choice of management of mutation carriers allows us to have a baseline for development of future studies of psychological impact of genetic testing and management related to genetic testing, so that these high risk families can be better supported. / published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

published_or_final_version / Social Work and Social Administration / Master / Master of Social Sciences

published_or_final_version / Social Work / Master / Master of Social Work

published_or_final_version / Social Work and Social Administration / Doctoral / Doctor of Philosophy

陳津利. / "2000年7月" / 論文 (哲學碩士)--香港中文大學, 2000. / 參考文獻 (leaves 138-151) / 附中英文摘要. / "2000 nian 7 yue" / Chen Jinli. / Lun wen (zhe xue shuo shi)--Xianggang Zhong wen da xue, 2000. / Can kao wen xian (leaves 138-151) / Fu Zhong Ying wen zhai yao. / Chapter 第一章 --- 緒論 --- p.1 / Chapter 第一節 --- 中國的乳腺癌患者 --- p.1 / Chapter 第二節 --- 中國內地的癌症自助團體 --- p.3 / Chapter 第三節 --- 硏究意義和主題 --- p.5 / Chapter 一、 --- 硏究意義 --- p.5 / Chapter 二、 --- 硏究主題 --- p.8 / Chapter 第二章 --- 文獻回顧 --- p.9 / Chapter 第一節 --- 乳腺癌和乳腺癌患者 --- p.9 / Chapter 一、 --- 乳腺癌和乳腺癌患者的定義 --- p.9 / Chapter 二、 --- 患者瀕死的心理反應 --- p.10 / Chapter 三、 --- 患者面臨的實際問題和情感需求 --- p.15 / Chapter 第二節 --- 支持的槪念和取向 --- p.21 / Chapter 一、 --- 社會支持的槪念 --- p.21 / Chapter 二、 --- 支持的類型 --- p.23 / Chapter 三、 --- 社會支持的功能 --- p.27 / Chapter 四、 --- 社會支持的測量和指標 --- p.31 / Chapter 第三節 --- 自助團體的定義及功能 --- p.36 / Chapter 一、 --- 自助團體的定義 --- p.36 / Chapter 二、 --- 自助團體作爲社會支持系統的組成部分 --- p.37 / Chapter 第三章 --- 硏究架構 --- p.46 / Chapter 第一節 --- 基本假設 --- p.46 / Chapter 第二節 --- 研究變量名詞的操作性定義 --- p.48 / Chapter 一、 --- 自助團體行爲認知 --- p.48 / Chapter 二、 --- 感受的情感支持 --- p.50 / Chapter 三、 --- 個人特徵 --- p.50 / Chapter 第四章 --- 硏究方法 --- p.51 / Chapter 第一節 --- 研究法的選擇 --- p.51 / Chapter 一、 --- 應用三角測量的思考 --- p.51 / Chapter 二、 --- 量化爲主、質性爲輔的主輔設計 --- p.51 / Chapter 三、 --- 同步三角測量法的采用 --- p.53 / Chapter 第二節 --- 問卷調查硏究設計 --- p.54 / Chapter 一、 --- 樣本策略_ --- p.54 / Chapter 二、 --- 測量工具 --- p.56 / Chapter 三、 --- 資料搜集方法 --- p.59 / Chapter 四、 --- 效度和信度 --- p.59 / Chapter 五、 --- 問卷調查的資料處理及數据分析 --- p.62 / Chapter 第三節 --- 質性硏究方案 --- p.63 / Chapter 一、 --- 硏究樣本及資料收集 --- p.63 / Chapter 二、 --- 資料分析 --- p.63 / Chapter 第四節 --- 硏究局限 --- p.65 / Chapter 第五章 --- 硏究結果 --- p.66 / Chapter 第一節 --- 中國乳腺癌患者的基本特徵 --- p.66 / Chapter 一、 --- 背景結構 --- p.66 / Chapter 二、 --- 身心狀況 --- p.72 / Chapter 三、 --- 病患情感特徵 --- p.77 / Chapter 第二節 --- 患者自助團體行爲認知 --- p.85 / Chapter 一、 --- 患者的自助團體活動參與程度(A1 ) --- p.85 / Chapter 二、 --- 患者的自助團體活動認知程度(A2 ) --- p.90 / Chapter 三、 --- 患者對自助團體的主觀認同(A3) --- p.91 / Chapter 四、 --- 個人基本特徵的作用 --- p.96 / Chapter 第三節 --- 患者自助團體中的情感支持感受(B) --- p.100 / Chapter 一、 --- 患者在自助團體中的情感支持感受 --- p.100 / Chapter 二、 --- 個人特徵對情感支持感受影響 --- p.108 / Chapter 第四節 --- 假設驗証：自助團體行爲認知與情感支持感受的 相關關係 --- p.114 / Chapter 一、 --- 活動參與程度(A1)與情感支持感受的相關關係 --- p.115 / Chapter 二、 --- 活動認知程度(A2)與情感支持感受的相關關係 --- p.119 / Chapter 三、 --- 主觀認同(A3)與情感支持感受的相關關係 --- p.120 / Chapter 四、 --- 個人基本特徵對行爲認知(A)與情感支持感受 關係的影響 --- p.122 / Chapter 五、 --- 小結 --- p.122 / Chapter 第六章 --- 結論、檢討及建議 --- p.123 / Chapter 第一節 --- 硏究結果討論 --- p.123 / Chapter 一、 --- 自助團體情感支持硏究結果與西方 研究的异同及討論 --- p.123 / Chapter 二、 --- 社會支持理論和槪念的适用性討論 --- p.127 / Chapter 第二節 --- 待5幵究或澄淸的議題 --- p.129 / Chapter 一、 --- 患者的情感問題： 乳腺癌是否破坏了患者的婚姻質量？ --- p.129 / Chapter 二、 --- 家庭的支持功能問題： 什么是對患者的“愛´ح ？ --- p.131 / Chapter 三、 --- 來自“大鍋飯´ح的資源： 制度安排帶給乳腺癌患者什么？ --- p.131 / Chapter 四、 --- 未接受乳房再造術： 經濟的？醫療的？制度的？觀念的？ --- p.132 / Chapter 五、 --- 關於自助團體的几點發現 --- p.132 / Chapter 第三節 --- 建議 --- p.134 / Chapter 一、 --- 政府部門與自助團體建立伙伴關係 --- p.134 / Chapter 二、 --- 加強對患者家庭的輔導，引進境外社會工 作理念和實務，開展針對性情感治療 --- p.134 / Chapter 三、 --- 營造新女性文化，關注自身生存質量 --- p.135 / Chapter 四、 --- 未來的硏究 --- p.136 / 參考書目 --- p.138 / 附錄 / 附錄一統計結果列表 --- p.152 / 附錄二 量表信度列表 --- p.173 / 附錄三調查問卷 --- p.177 / 附錄四訪談指引 --- p.185

published_or_final_version / abstract / Pathology / Doctoral / Doctor of Philosophy

Tse Man. / Accompanying booklet titled: Dietary assessment food portion booklet. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 101-122). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / Abstract (Chinese version) --- p.iv / Table of contents --- p.vi / List of figures --- p.x / List of tables --- p.xi / List of abbreviations --- p.xiv / Chapter Chapter one: --- Introduction --- p.1 / Breast cancer trends in Hong Kong --- p.1 / Risk factors for breast cancer occurrence --- p.4 / "Body weight, obesity, hormones and breast cancer" --- p.4 / Evidence for postmenopausal women --- p.4 / Evidence for premenopausal women --- p.6 / Hormones and breast cancer --- p.7 / Dietary factors: Foods and nutrients --- p.11 / Animal foods and fats --- p.11 / Dietary fats --- p.13 / Other animal foods --- p.14 / Fruit and vegetable intakes --- p.14 / Positive family history --- p.15 / Alcohol consumption and cigarette smoking --- p.15 / Physical Activity --- p.17 / "Cancer, obesity and immunity" --- p.17 / Aims and scope of the study --- p.19 / Chapter Chapter two: --- Methodology --- p.22 / Questionnaires and their derivation --- p.22 / Literature derivation of the questionnaires --- p.22 / Pretest of the questionnaires --- p.25 / Research ethics --- p.26 / Subject recruitment --- p.26 / Anthropometric measurements --- p.27 / Interviews --- p.28 / First interview --- p.28 / Second and third telephone interviews --- p.29 / Immunoassays --- p.30 / Materials for immunoassays --- p.30 / Immunophenotyping of cells --- p.30 / MultiTEST´ёØ four-color direct immunofluorescence reagent kit --- p.32 / Human tumor neurosis factor-alpha (TNF-α) Quantikine® high sensitivity enzyme-linked immunosorbent assay (ELISA) kit --- p.33 / Methods for immunoassays --- p.33 / Flow cytometric analysis --- p.34 / TNF-α Quantikine® high sensitivity ELISA assay --- p.35 / Data management --- p.35 / Statistical methods --- p.35 / Data analysis --- p.36 / Dietary analysis --- p.36 / Definition of weight status --- p.37 / Measurements of immune cell levels --- p.37 / Chapter Chapter three: --- Results --- p.39 / Participation rate --- p.39 / Characteristics of the patients --- p.40 / Demographics --- p.40 / Pregnancy and breast-feeding experiences --- p.42 / Medical history --- p.43 / Body weight and obesity status --- p.45 / Dietary patterns --- p.46 / Fat and oil removal habit when eating meat and poultry --- p.46 / Perceived fat consumption --- p.46 / Eating out habits --- p.47 / Vegetarian diet adoption and food allergy or intolerance --- p.48 / Cooking methods --- p.48 / Alcohol consumption and supplementation habits --- p.50 / Preferences and perceived amounts of consumption on food groups --- p.51 / Cooking oils used at home --- p.52 / Nutrient intake patterns from dietary recalls --- p.53 / Soy intakes --- p.55 / Meal locations --- p.55 / Energy intakes by weight status --- p.56 / Food group intakes by FFQ --- p.57 / Food items not covered by FFQ --- p.62 / Top ten fat and fiber contributors by FFQ --- p.63 / Daily fruit and vegetable intakes by FFQ and 3 days' dietary recalls --- p.64 / Correlation of FFQ and 3 days' dietary recalls by food group intakes --- p.64 / Correlation of FFQ and 3 days' dietary recalls by fat and fiber intakes --- p.65 / Fat and fiber intakes by weight status --- p.66 / Other lifestyle patterns --- p.68 / Exercise participation and smoking habits --- p.68 / Daily activities' participation by weight status --- p.69 / Immune status / Overview of general immune cell levels --- p.71 / Immune status and BMI weight grouping --- p.72 / Immune status and overweight --- p.74 / Immune status and percent body fat --- p.76 / Immune status and waist-hip ratio --- p.77 / "Weight status, adiposity and immune status: summary" --- p.78 / Immune status and protein intakes --- p.82 / Immune status and fat intakes --- p.83 / Immune status and fiber intake --- p.84 / Immune status and vitamin C intake --- p.85 / Immune status and menopausal status --- p.86 / Chapter Chapter four: --- Discussion / Implications of findings --- p.88 / Interpreting the Immune status of the subjects --- p.88 / Lymphocyte and NK cell levels --- p.89 / Regulatory T cell (Treg) levels --- p.89 / TNF-α levels --- p.90 / Immune status and nutrient intakes --- p.90 / Typical dietary patterns of the subjects --- p.91 / Physical activity patterns --- p.94 / Weight status --- p.95 / "Subjects' fat, fiber intakes and anthropometric measurements compared to previous research" --- p.96 / Limitations of the study --- p.96 / Future directions of research --- p.98 / Chapter Chapter five: --- Conclusion --- p.99 / References --- p.101 / Appendices --- p.123 / Chapter A1 --- Questionnaire (Chinese version) --- p.123 / Chapter A2 --- Questionnaire (English version) --- p.138 / Chapter B1 --- Food frequency questionnaire (Chinese version) --- p.153 / Chapter B2 --- Food frequency questionnaire (English version) --- p.156 / Chapter C --- Dietary assessment food portion booklet --- p.160 / Chapter D1 --- 3 days dietary recall questionnaire (Chinese version) --- p.161 / Chapter D2 --- 3 days dietary recall questionnaire (English version) --- p.174 / Chapter El --- Consent form (Chinese version) --- p.187 / Chapter E2 --- Consent form (English version) --- p.189 / Chapter F --- Results of patient invitation to participate during recruitment period --- p.191