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標題: 運用蛋白質胼合物作為生物指標探討乳癌風險因子與體內雌性激素與萘苯醌累積劑量之相關性分析
Associations of the risk factors of breast cancer with cumulative body burden of estrogen and naphthalene quinones using protein adducts as biomarkers
作者: 葛茂輝
Ko, Mao-Hui
關鍵字: 生物指標
Protein adduct

出版社: 環境工程學系所
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摘要: 本研究目的為測量台灣中部地區女性乳癌病人 (n=67)體內血清白蛋白中雌性激素及萘醌類蛋白質胼合物之背景值及與乳癌風險因子 (年齡、身體質量指標及單一核苷酸基因多型性)間之相關性分析討論。分析結果顯示,乳癌病人 (n=67)體內血清白蛋白E2-2,3-quinone (E2-2,3-Q-4-S-Alb)及 E2-3,4-quinone (E2-3,4-Q-2-S-Alb)所偵測之平均背景值 (標準偏差)分別為393 (263) 及 681 (330) pmol/g。此外,1,2-NPQ-Alb 及1,4-NPQ-Alb 所偵測之平均背景值 (標準偏差)分別為237 (130) 及 78.3 (47.5) pmol/g。1,2-NPQ-Alb 及1,4-NPQ-Alb 具有中度正相關且達顯著差異(r=0.420, p < 0.001)。E2-2,3-Q-4-S-Alb及E2-3,4-Q-2-S-Alb 具有高度正相關且達顯著差異(r=0.707, p < 0.001)。將本研究數據加入先前實驗室所分析之樣本 (n=85)共同討論後發現,在年齡小於50歲且Body Mass Index (BMI)小於27之乳癌病人族群中,其BMI與E2-3,4-Q-2-S-Alb 之背景值呈負相關性 (r=-0.241,p<0.05)。另一方面,乳癌病人(n=152) 中萘醌類蛋白質胼合物1,2-NPQ-Alb與年齡呈現正相關性且達顯著差異 (r=0.266,P<0.001)。而乳癌病人體內之萘醌類蛋白質胼合物1,2-NPQ-Alb之背景值在BMI大於27之族群中高於BMI小於27之族群約30%。另外,本研究結果顯示乳癌患者相較於實驗室先前分析多個之無罹患乳癌樣本,其E2-3,4-Q-2-S-Alb與E2-2,3-Q-4-S-Alb背景值之比值約高出4倍。本研究之結論為乳癌患者體內E2-3,4-Q-2-S-Alb之體內累積劑量為一乳癌風險之預測指標。
The aims of this study were to measure the background level of 17B-estradiol (E2) and naphthalene quinone (NPQ)-derived protein adducts in human albumin (Alb) derived from female breast cancer patients (n=67) in central Taiwanese women and to explore the relationships between these adducts with risk factors of breast cancer (Age, Body Mass Index, Single Nucleotide Polymorphism). Results from the analysis indicated that Alb adducts of estrogen quinones, including E2-2,3-quinone (E2-2,3-Q-4-S-Alb) and E2-3,4-quinone (E2-3,4-Q-2-S-Alb) were detected in all subjects (n=67) at average levels were 393 (263) and 681 (330) pmol/g, respectively. In addition, the average levels of cysteinyl adducts of 1,2-NPQ and 1,4-NPQ on human serum albumin were estimated to be 237 (130) and 78.3 (47.5) pmol/g, respectively. Levels of 1,4-NPQ-Alb correlated significantly with those of 1,2-NPQ-Alb (r=0.420, p < 0.001). Similarly, levels of E2-2,3-Q-4-S-Alb correlated significantly with those of E2-3,4-Q-2-S-Alb (r=0.707, p < 0.001). When comparing these data with our previous study (n=85), we noticed that among those breast cancer patients with age under 50 and BMI less than 27, BMI inversely associated with E2-3,4-Q-2-S-Alb (r=-0.241,p<0.05). Additionally, levels of 1,2-NPQ-Alb positively correlated with age (r=0.266,P<0.001). Levels of 1,2-NPQ-Alb in patients with BMI over 27 were 30% higher than patients with BMI under 27. We noteced that the ratio of E2-3,4-Q-Alb and E2-2,3-Q-Alb derived adducts in breast cancer patients were ~4 fold greater than those of controls. This evidence suggests that the cumulative body burden of E2-3,4-Q is a significant indicator of the risk of breast cancer.
其他識別: U0005-1607201217262700
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