Please use this identifier to cite or link to this item:
標題: 運用雌激素醌類代謝物蛋白質胼合物作為子宮內膜癌預防醫學之生物指標
Application of estrogen quinone-derived protein adducts as biomarkers of Endometrial cancer in preventive medicine.
作者: 林昱廷
Yu-Ting Lin
關鍵字: 子宮內膜癌;子宮肌瘤;雌激素;Endometrial cancer;Leiomyoma;estrogen
引用: Board, P.D.Q.A.T.E., 2002. Endometrial Cancer Treatment (PDQ(R)): Patient Version. PDQ Cancer Information Summaries. National Cancer Institute (US), Bethesda (MD). Bolton, J.L., Thatcher, G.R., 2008. Potential mechanisms of estrogen quinone carcinogenesis. Chem Res Toxicol 21, 93-101. Butterworth, M., Lau, S.S., Monks, T.J., 1996. 17 beta-Estradiol metabolism by hamster hepatic microsomes. Implications for the catechol-O-methyl transferase-mediated detoxication of catechol estrogens. Drug metabolism and disposition: the biological fate of chemicals 24, 588-594. Cavalieri, E., Chakravarti, D., Guttenplan, J., Hart, E., Ingle, J., Jankowiak, R., Muti, P., Rogan, E., Russo, J., Santen, R., Sutter, T., 2006. Catechol estrogen quinones as initiators of breast and other human cancers: Implications for biomarkers of susceptibility and cancer prevention. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1766, 63-78. Cavalieri, E., Rogan, E., 2014. The molecular etiology and prevention of estrogen-initiated cancers: Ockham's Razor: Pluralitas non est ponenda sine necessitate. Plurality should not be posited without necessity. Molecular Aspects of Medicine 36, 1-55. Cavalieri, E.L., Rogan, E.G., 2011. Unbalanced metabolism of endogenous estrogens in the etiology and prevention of human cancer. J Steroid Biochem 125, 169-180. Cavalieri, E.L., Stack, D.E., Devanesan, P.D., Todorovic, R., Dwivedy, I., Higginbotham, S., Johansson, S.L., Patil, K.D., Gross, M.L., Gooden, J.K., Ramanathan, R., Cerny, R.L., Rogan, E.G., 1997. Molecular origin of cancer: catechol estrogen-3,4-quinones as endogenous tumor initiators. Proc Natl Acad Sci U S A 94, 10937-10942. Clapp, R.W., Jacobs, M.M., Loechler, E.L., 2008. Environmental and Occupational Causes of Cancer New Evidence, 2005–2007. Reviews on environmental health 23, 1-37. Convert, O., Van Aerden, C., Debrauwer, L., Rathahao, E., Molines, H., Fournier, F., Tabet, J.C., Paris, A., 2002. Reactions of estradiol-2,3-quinone with deoxyribonucleosides: possible insights in the reactivity of estrogen quinones with DNA. Chem Res Toxicol 15, 754-764. Dawling, S., Roodi, N., Mernaugh, R.L., Wang, X.H., Parl, F.F., 2001. Catechol-O-methyltransferase (COMT)-mediated metabolism of catechol estrogens: Comparison of wild-type and variant COMT isoforms. Cancer research 61, 6716-6722. Eggemann, H., Ignatov, T., Burger, E., Costa, S.D., Ignatov, A., 2017. Management of elderly women with endometrial cancer. Gynecologic Oncology 146, 519-524. Ehrenberg, L., H., K. D., Osterman-Golkar, S., W., I., 1974. Evaluation of genetic risks of alkylating agents: tissue doses in the mouse from air contaminated with ethylene oxide. Mutation Research. 24, 83-103. Galaal, K., Al Moundhri, M., Bryant, A., Lopes, A.D., Lawrie, T.A., 2014. Adjuvant chemotherapy for advanced endometrial cancer. The Cochrane database of systematic reviews, Cd010681. Hanna, W.M., Ruschoff, J., Bilous, M., Coudry, R.A., Dowsett, M., Osamura, R.Y., Penault-Llorca, F., van de Vijver, M., Viale, G., 2014. HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 27, 4-18. Hayes, C.L., Spink, D.C., Spink, B.C., Cao, J.Q., Walker, N.J., Sutter, T.R., 1996. 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. P Natl Acad Sci USA 93, 9776-9781. Jiang, H., Wang, B., Zhang, F., Qian, Y., Chuang, C.C., Ying, M., Wang, Y., Zuo, L., 2016. The Expression and Clinical Outcome of pCHK2-Thr68 and pCDC25C-Ser216 in Breast Cancer. International journal of molecular sciences 17. Johnatty, S.E., Tan, Y.Y., Buchanan, D.D., Bowman, M., Walters, R.J., Obermair, A., Quinn, M.A., Blomfield, P.B., Brand, A., Leung, Y., Oehler, M.K., Kirk, J.A., O'Mara, T.A., Webb, P.M., Spurdle, A.B., 2017. Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling. Gynecologic Oncology 147, 381-387. Lin, C., Chen, D.R., Hsieh, W.C., Yu, W.F., Lin, C.C., Ko, M.H., Juan, C.H., Tsuang, B.J., Lin, P.H., 2013. Investigation of the cumulative body burden of estrogen-3,4-quinone in breast cancer patients and controls using albumin adducts as biomarkers. Toxicol Lett 218, 194-199. Lin, C., Hsieh, W.-C., Chen, D.-R., Kuo, S.-J., Yu, W.-F., Hu, S.-W., Sue, H.-J., Ko, M.-H., Juan, C.-H., Chung, K.-S., Lin, P.-H., 2014. Hemoglobin adducts as biomarkers of estrogen homeostasis: Elevation of estrogenquinones as a risk factor for developing breast cancer in Taiwanese Women. Toxicology Letters 225, 386-391. MacNab, W., Mehasseb, M.K., 2016. Endometrial cancer. Obstetrics, Gynaecology & Reproductive Medicine 26, 193-199. Minghetti, P.P., Ruffner, D.E., Kuang, W.J., Dennison, O.E., Hawkins, J.W., Beattie, W.G., Dugaiczyk, A., 1986. Molecular structure of the human albumin gene is revealed by nucleotide sequence within q11-22 of chromosome 4. Journal of Biological Chemistry 261, 6747-6757. Morice, P., Leary, A., Creutzberg, C., Abu-Rustum, N., Darai, E., 2016. Endometrial cancer. The Lancet 387, 1094-1108. Nagle, C.M., Crosbie, E.J., Brand, A., Obermair, A., Oehler, M.K., Quinn, M., Leung, Y., Spurdle, A.B., Webb, P.M., 2018. The association between diabetes, comorbidities, body mass index and all-cause and cause-specific mortality among women with endometrial cancer. Gynecologic Oncology 150, 99-105. Pěnčíková, K., Svržková, L., Strapáčová, S., Neča, J., Bartoňková, I., Dvořák, Z., Hýžďalová, M., Pivnička, J., Pálková, L., Lehmler, H.-J., Li, X., Vondráček, J., Machala, M., 2018. In vitro profiling of toxic effects of prominent environmental lower-chlorinated PCB congeners linked with endocrine disruption and tumor promotion. Environmental Pollution 237, 473-486. Saso, S., Chatterjee, J., Georgiou, E., Ditri, A.M., Smith, J.R., Ghaem-Maghami, S., 2011. Endometrial cancer. BMJ 343. Sonoda, Y., Barakat, R.R., 2006. Screening and the prevention of gynecologic cancer: Endometrial cancer. Best Practice & Research Clinical Obstetrics & Gynaecology 20, 363-377. Spink, D.C., Spink, B.C., Cao, J.Q., Gierthy, J.F., Hayes, C.L., Li, Y., Sutter, T.R., 1997. Induction of cytochrome P450 1B1 and catechol estrogen metabolism in ACHN human renal adenocarcinoma cells. J Steroid Biochem Mol Biol 62, 223-232. Srijaipracharoen, S., Tangjitgamol, S., Tanvanich, S., Manusirivithaya, S., Khunnarong, J., Thavaramara, T., Leelahakorn, S., Pataradool, K., 2010. Expression of ER, PR and Her-2/neu in Endometrial Cancer: A Clinicopathological Study. pp. 215-220. Törnqvist, M., Fred, C., Haglund, J., Helleberg, H., Paulsson, B., Rydberg, P., 2002. Protein adducts: quantitative and qualitative aspects of their formation, analysis and applications. Journal of Chromatography B 778, 279-308. Tarney, C.M., Tian, C., Wang, G., Dubil, E.A., Bateman, N.W., Chan, J.K., Elshaikh, M.A., Cote, M.L., Schildkraut, J.M., Shriver, C.D., Conrads, T.P., Hamilton, C.A., Maxwell, G.L., Darcy, K.M., 2018. Impact of age at diagnosis on racial disparities in endometrial cancer patients. Gynecologic Oncology 149, 12-21. Terry, P.D., Rohan, T.E., Franceschi, S., Weiderpass, E., 2002. Cigarette smoking and the risk of endometrial cancer. The Lancet Oncology 3, 470-480. Tornqvist, M., Fred, C., Haglund, J., Helleberg, H., Paulsson, B., Rydberg, P., 2002. Protein adducts: quantitative and qualitative aspects of their formation, analysis and applications. J Chromatogr B Analyt Technol Biomed Life Sci 778, 279-308. Turesky, R.J., Le Marchand, L., 2011. Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines. Chem Res Toxicol 24, 1169-1214. Willing, C., Peich, M., Danescu, A., Kehlen, A., Fowler, P.A., Hombach-Klonisch, S., 2011. Estrogen-independent actions of environmentally relevant AhR-agonists in human endometrial epithelial cells. MHR: Basic science of reproductive medicine 17, 115-126. Yager, J.D., 2015. Mechanisms of estrogen carcinogenesis: The role of E2/E1-quinone metabolites suggests new approaches to preventive intervention--A review. Steroids 99, 56-60. Yang, H.P., Brinton, L.A., Platz, E.A., Lissowska, J., Lacey, J.V., Sherman, M.E., Peplonska, B., Garcia-Closas, M., 2010. Active and passive cigarette smoking and the risk of endometrial cancer in Poland. European Journal of Cancer 46, 690-696. Yudt, M.R., Russo, L.A., Berrodin, T.J., Jelinsky, S.A., Ellis, D., Cohen, J.C., Cooch, N., Haglund, E., Unwalla, R.J., Fensome, A., Wrobel, J., Zhang, Z., Nagpal, S., Winneker, R.C., 2011. Discovery of a novel mechanism of steroid receptor antagonism: WAY-255348 modulates progesterone receptor cellular localization and promoter interactions. Biochemical pharmacology 82, 1709-1719. Zhu, Y., Lu, D., Lira, M.E., Xu, Q., Du, Y., Xiong, J., Mao, M., Chung, H.C., Zheng, G., 2016. Droplet digital polymerase chain reaction detection of HER2 amplification in formalin fixed paraffin embedded breast and gastric carcinoma samples. Experimental and molecular pathology 100, 287-293.
17β-雌二醇-2,3-醌 (E2-2,3-Q) 和17β-雌二醇-3,4-醌 (E2-3,4-Q) 為雌性激素活性代謝物,被認為是誘發基因毒性之主因。本研究的目的是分析正常人 (n = 20),子宮肌瘤病人 (n = 20) 以及子宮內膜癌病人 (n = 20) 之雌性激素醌類代謝物血清白蛋白胼合物,並利用雌性激素醌類代謝物血清白蛋白胼合物之背景值建立台灣女性子宮內膜癌預測模式之研究。其中生物指標包含E2-3,4-Q-2-S-Alb,E2-2,3-Q-4-S-Alb 以及E2-3,4-Q-2-S-Alb和E2-2,3-Q-4-S-Alb這三個指標,以通過混合模式篩選罹患子宮內膜癌之高風險族群。
混合模型利用統合正常人,子宮肌瘤病人以及子宮內膜癌病人之雌性激素醌類代謝物血清白蛋白胼合物背景值。計算雌性激素醌類代謝物血清白蛋白胼合物之平均值,並作為子宮內膜癌風險 (高風險和低風險之指標)。比較每個族群個體間年齡以及BMI之特徵。並且,估計篩選模式之預測值,偽陽性 (False positive)以及偽陰性 (False negative) 之比率。
結果顯示,正常人、子宮肌瘤病人以及子宮內膜癌病人之雌性激素醌類代謝物蛋白質胼合物E2-3,4-Q-2-S-Alb以及E2-2,3-Q-4-S-Alb之背景值。其中E2-3,4-Q-2-S-Alb與E2-2,3-Q-4-S-Alb (n = 60) 具有顯著相關性 (r = 0.915,p <0.001)。 總體而言,此一研究結果顯示,雌性激素醌類代謝物血清白蛋白胼合物之背景值與子宮內膜癌之風險無關。未來有必要再進一步調查以驗證這些初步結果。

Both 17β-estradiol-2,3-quinone (E2-2,3-Q) and 17β-estradiol-3,4-quinone (E2-3,4-Q) are reactive metabolites of estrogen that are thought to be responsible for the estrogen-induced genotoxicity. The aim of this study was to analyze estrogen quinone-derived adducts in albumin (Alb) derived from, healthy controls (n=20), leiomyoma patients (n=20), and endometrial cancer patients (n=20) and to establish a prediction model of endometrial cancer by using the background values of estrogen quinone-derived Alb adducts in Taiwanese women. The biomarkers included 3 indicators, i.e., E2-3,4-Q-2-S-Alb, E2-2,3-Q-4-S-Alb, and summation of E2-3,4-Q-2-S-Alb and E2-2,3-Q-4-S-Alb, to screen for high risk individuals of developing endometrial cancer by the mixed model.
Mixed model utilizes the background levels of protein adducts derived from the combined pool of healthy controls, leiomyoma patients, and endometrial cancer patients. The mean values of estrogen quinone-derived Alb adducts were calculated and served as indicators of endometrial cancer risk (high and low risk). Subjects' characteristics for each group of individuals in terms of age and BMI were compared. Additionally, the predictive values, false positive rates, and false negative rates of the screening model were estimated..
Results confirmed that levels of estrogen quinone-derived adducts, including E2-3,4-Q-2-S-Alb and E2-2,3-Q-4-S-Alb, were detected in all three groups of subjects. Levels of E2-3,4-Q-2-S-Alb correlated significantly with those of E2-2,3-Q-4-S-Alb (n=60) (correlation coefficient r= 0.915, p<0.001). Overall, this evidence suggests that the levels of these adducts in human Alb did not associate with risk of developing endometrial cancer. Further investigation is warranted to verify these preliminary findings.
Rights: 同意授權瀏覽/列印電子全文服務,2018-08-13起公開。
Appears in Collections:環境工程學系所

Files in This Item:
File SizeFormat Existing users please Login
nchu-107-7105063126-1.pdf2.42 MBAdobe PDFThis file is only available in the university internal network   
Show full item record

Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.