臺灣博碩士論文加值系統

乳癌是台灣女性中最常見癌症之一。人們認為環境因素，例如。飲食，年齡，可能導致雌激素穩態失衡及隨後發生乳癌之風險增加。因此，（1）使用高預測標記物篩選具有高乳癌風險之族群和（2）開發用於乳腺癌診斷和標的治療之新型生物標誌物在乳腺癌研究之預防和臨床醫學領域中是至關重要。
本研究之目的是使用台灣孕婦中17β-雌二醇（E2）醌衍生蛋白胼合物之背景水平，驗證混合模型對乳癌預測之預測價值。生物標誌物包括3個指標，即E2-3,4-Q-2-S-Hb，E2-2,3-Q-4-S-Hb和E2-3,4-Q-2-S-Hb+ E2-2,3-Q-4-S-Hb用於通過“混合模型”方法篩選罹患乳癌之高風險個體。
混合模型利用來自乳癌患者和健康對照組織這些雌激素醌胼合物之背景水平。計算這些雌激素醌衍生之Hb胼合物之算術平均值和分位數值，並作為乳癌風險之指標（高風險組和低風險組）。受試者對每組個體之特徵，例如 年齡和BMI進行了比較。另外，估計了預測正確值，偽陽性及偽陰性值。
結果表明，使用這三種Hb胼合物作為指標之混合模型對台灣孕婦預測正確值大於99％。綜合以上之研究顯示，運用Hb胼合物作為指標建立之混合模型將能夠作為篩選台灣女性罹患乳癌之高風險族群，並將在乳癌預防醫學領域做出貢獻。

Breast cancer is one of the most prevalent cancers among Taiwanese women. It is believed that environmental factors, eg. diet, age, may lead to imbalances in estrogen homeostatsis and subsequent increased risk of developing breast cancer. Thus, (1) to screen for population with high risk of developing breast cancer using high predicative markers and (2) to develop novel biomarkers for diagnosis and target therapy of breast cancer is critical in the field of preventive and clinical medicine in breast cancer research.
The purpose of this study was to verify the predictive value of the Mixed model for breast cancer prediction using the background levels of 17β-estradiol (E2) quinone-derived protein adducts in Taiwanese pregnant women. The biomarkers included 3 indicators, i.e., E2-3,4-Q-2-S-Hb, E2-2,3-Q-4-S-Hb, and E2-3,4-Q-2-S-Hb+E2-2,3-Q-4-S-Hb, were used to screen for high risk individuals of developing breast cancer by the “Mixed Model” approach.
The Mixed model utilizes the background levels of these estrogen quinone adducts derived from the combined pool of breast cancer patients and healthy controls. The arithmatic means and quantile values of these estrogen quinone-derived Hb adducts were calculated and served as indicators of breast cancer risk (high and low risk groups). Subjects’ characteristics for each group of individuals, eg. age and BMI, were compared. Additionally, the predictive values, false positive rates, and false negative rates were estimated.
Results indicated that the predicative values of the Mixed model for Taiwanese pregnant women using these three Hb adducts as indicators were greater than 99%. We concluded that the Mixed model we established using Hb adducts as indicators will be able to screen for population with high risk of developing breast cancer in Taiwanese women and will make a contribution in the field of preventive medicine of breast cancer.

摘要 i
Abstract ii
縮寫表 (List of Abbreviation) iii
目錄 iv
圖目錄 vi
表目錄 viii
第一章　前言 1
1-1 研究緣起 1
1-2 研究目的 2
第二章　文獻回顧 3
2-1乳癌 3
2-1-1 台灣罹患乳癌現況 4
2-1-2 乳癌高風險族群 7
2-1-3 雌激素與乳癌之相關性 8
2-2 雌激素 10
2-2-1 雌激素代謝機制 11
2-3 生物指標 13
2-3-1環境醫學中之廣泛運用生物指標 (Biomarker) 13
2-3-2蛋白質胼合物作為生物指標 14
2-3-3採用紅血球蛋白質胼合物作為人體之生物指標 17
第三章　實驗架構與研究假設 19
3-1 實驗架構 19
3-1-1雌激素醌類代謝物紅血球蛋白質胼合物檢測 19
3-2 篩選流程 20
3-2-1 Mixed Model (混合模式) 算數平均數以及標準偏差 20
3-2-2Mixed Model (混合模式) 四分位數 21
3-3 研究假設 22
第四章　實驗方法 23
4-1驗證方法 23
4-1-1 Mixed Model (混合模式) 算數平均數以及標準偏差 23
4-1-2 Mixed Model (混合模式) 四分位數 25
4-2 國家衛生研究院提供之懷孕婦女基本資料 26
第五章　實驗結果 33
5-1 彰化基督教醫院乳癌病人之背景值以及大千醫院正常人背景值之模式架構驗證結果 33
5-2混合模式之算數平均數及標準偏差族群分佈 35
5-3 混合模式之四分位數族群分佈 41
第六章　討論 47
6-1 混合模式下算數平均數及四分位數之預測值驗證結果 48
6-2 雌激素醌類代謝物紅血球蛋白質胼合物作為乳癌指標之專一性 50
6-3 篩選乳癌高風險族群之生物指標模式之適用性 52
第七章　結論 53
第八章　未來工作 54
第九章　參考文獻 55

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