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標題: 探討乳癌病患身體質量指數及雌性激素代謝活化基因之多型性與白血球去鹼基核酸背景值之相關性
Investigation of the association of body mass index and polymorphisms of genes responsible for estrogen bioactivation with the background levels of abasic sites in white blood cells derived from breast cancer patients
作者: 劉致辰
Liu, Chin-Chen
關鍵字: breast cancer;去鹼基核酸;abasic site;single nucleotide polymorphism;單一核苷酸基因多型性
出版社: 環境工程學系所
引用: 林慶全 (2011) 運用血清白蛋白胼合物為生物指標探討體內累積之雌性激素-3,4-苯醌代謝物作為乳癌風險預測指標之研究。國立中興大學環境工程研究所碩士論文,台灣台中。 蘇弘傑 (2011) 運用血紅蛋白胼合物為生物指標評估多環芳香族碳氫化合物之環境暴露與體內累積之雌性激素醌類代謝物相關性之研究。國立中興大學環境工程研究所碩士論文,台灣台中。 Bailey, L.R., Roodi, N., Verrier, C.S., Yee, C.J., Dupont, W.D., Parl, F.F., 1998. Breast cancer and CYPIA1, GSTM1, and GSTT1 polymorphisms: evidence of a lack of association in Caucasians and African Americans. Cancer Res 58, 65-70. Bernstein, L., Ross, R.K., 1993. Endogenous hormones and breast cancer risk. Epidemiol Rev 15, 48-65. Bhattacharyya, K.K., Brake, P.B., Eltom, S.E., Otto, S.A., Jefcoate, C.R., 1995. Identification of a rat adrenal cytochrome P450 active in polycyclic hydrocarbon metabolism as rat CYP1B1. Demonstration of a unique tissue-specific pattern of hormonal and aryl hydrocarbon receptor-linked regulation. J Biol Chem 270, 11595-11602. Boiteux, S., Guillet, M., 2004. Abasic sites in DNA: repair and biological consequences in Saccharomyces cerevisiae. DNA Repair 3, 1-12. Brüning, T., Abel, J., Koch, B., Lorenzen, K., Harth, V., Donat, S., Sachinidis, A., Vetter, H., Bolt, H.M., Ko, Y., 1999. Real-time PCR-analysis of the cytochrome P450 1B1 codon 432-polymorphism. Archives of Toxicology 73, 427-430. 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. Chen, D.-R., Chen, S.-T., Wang, T.-W., Tsai, C.-H., Wei, H.-H., Chen, G.-J., Yang, T.-C., Lin, C., Lin, P.-H., 2011. Characterization of estrogen quinone-derived protein adducts and their identification in human serum albumin derived from breast cancer patients and healthy controls. Toxicology Letters 202, 244-252. Chen, S., Xue, K., Xu, L., Ma, G., Wu, J., 2001. Polymorphisms of the CYP1A1 and GSTM1 genes in relation to individual susceptibility to lung carcinoma in Chinese population. Mutat Res 458, 41-47. Chetrite, G.S., Cortes-Prieto, J., Philippe, J.C., Wright, F., Pasqualini, J.R., 2000. Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol 72, 23-27. Christmann, M., Tomicic, M.T., Roos, W.P., Kaina, B., 2003. Mechanisms of human DNA repair: an update. Toxicology 193, 3-34. Cooke, M.S., Evans, M.D., Dizdaroglu, M., Lunec, J., 2003. Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 17, 1195-1214. Crofts, F., Taioli, E., Trachman, J., Cosma, G.N., Currie, D., Toniolo, P., Garte, S.J., 1994. Functional significance of different human CYP1A1 genotypes. Delort, L., Satih, S., Kwiatkowski, F., Bignon, Y.J., Bernard-Gallon, D.J., 2010. Evaluation of breast cancer risk in a multigenic model including low penetrance genes involved in xenobiotic and estrogen metabolisms. Nutr Cancer 62, 243-251. Diaz, L.K., Sneige, N., 2005. Estrogen receptor analysis for breast cancer: current issues and keys to increasing testing accuracy. Adv Anat Pathol 12, 10-19. Diergaarde, B., Potter, J.D., Jupe, E.R., Manjeshwar, S., Shimasaki, C.D., Pugh, T.W., DeFreese, D.C., Gramling, B.A., Evans, I., White, E., 2008. Polymorphisms in Genes Involved in Sex Hormone Metabolism, Estrogen Plus Progestin Hormone Therapy Use, and Risk of Postmenopausal Breast Cancer. Cancer Epidemiology Biomarkers & Prevention 17, 1751-1759. Doyle, A., Yager, J., 2008. Catechol-O-methyltransferase: Effects of the val108met polymorphism on protein turnover in human cells. Biochimica et Biophysica Acta (BBA) - General Subjects 1780, 27-33. Eliassen, A.H., Colditz, G.A., Rosner, B., Willett, W.C., Hankinson, S.E., 2006. Adult weight change and risk of postmenopausal breast cancer. JAMA 296, 193-201. Ferrer, J., Neyro, J.L., Estevez, A., 2005. Identification of risk factors for prevention and early diagnosis of a-symptomatic post-menopausal women. Maturitas 52 Suppl 1, S7-22. Fisher, D.A., 1998. Endocrinology Test Selection and Interpretation. Friedenreich, C.M., 2001. Review of anthropometric factors and breast cancer risk. Eur J Cancer Prev 10, 15-32. Gruber, C.J., Tschugguel, W., Schneeberger, C., Huber, J.C., 2002. Production and actions of estrogens. N Engl J Med 346, 340-352. Harth, V., Bruning, T., Abel, J., Koch, B., Berg, I., Sachinidis, A., Bolt, H.M., Vetter, H., Ko, Y., 2001. Real-time genotyping of cytochrome P4501A1 A4889G and T6235C polymorphisms. Mol Cell Probes 15, 93-97. Hazra, T.K., Izumi, T., Kow, Y.W., Mitra, S., 2003. The discovery of a new family of mammalian enzymes for repair of oxidatively damaged DNA, and its physiological implications. Carcinogenesis 24, 155-157. Huang, C.S., Chern, H.D., Chang, K.J., Cheng, C.W., Hsu, S.M., Shen, C.Y., 1999a. Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. Cancer Res 59, 4870-4875. Huang, C.S., Shen, C.Y., Chang, K.J., Hsu, S.M., Chern, H.D., 1999b. Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan. Br J Cancer 80, 1838-1843. Hunter, D.J., Colditz, G.A., Hankinson, S.E., Malspeis, S., Spiegelman, D., Chen, W., Stampfer, M.J., Willett, W.C., 2010. Oral contraceptive use and breast cancer: a prospective study of young women. Cancer Epidemiol Biomarkers Prev 19, 2496-2502. Ide, H., Kotera, M., 2004. Human DNA glycosylases involved in the repair of oxidatively damaged DNA. Biol Pharm Bull 27, 480-485. Izumi, T., 2003. Mammalian DNA base excision repair proteins: their interactions and role in repair of oxidative DNA damage. Toxicology 193, 43-65. Jackson, S.P., Bartek, J., 2009. The DNA-damage response in human biology and disease. Nature 461, 1071-1078. Jefcoate, C.R., Liehr, J.G., Santen, R.J., Sutter, T.R., Yager, J.D., Yue, W., Santner, S.J., Tekmal, R., Demers, L., Pauley, R., Naftolin, F., Mor, G., Berstein, L., 2000. Tissue-specific synthesis and oxidative metabolism of estrogens. J Natl Cancer Inst Monogr, 95-112. Jong, M.M.d., Nolte, I.M., Meerman, G.J.t., Graaf, W.T.A.v.d., Oosterwijk, J.C., Kleibeuker, J.H., Schaapveld, M., Vries, E.G.E.d., 2002. Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility. Kelsey, J.L., Bernstein, L., 1996. Epidemiology and prevention of breast cancer. Annu Rev Public Health 17, 47-67. Key, T.J., Appleby, P.N., Reeves, G.K., Roddam, A., Dorgan, J.F., Longcope, C., Stanczyk, F.Z., Stephenson, H.E., Jr., Falk, R.T., Miller, R., Schatzkin, A., Allen, D.S., Fentiman, I.S., Wang, D.Y., Dowsett, M., Thomas, H.V., Hankinson, S.E., Toniolo, P., Akhmedkhanov, A., Koenig, K., Shore, R.E., Zeleniuch-Jacquotte, A., Berrino, F., Muti, P., Micheli, A., Krogh, V., Sieri, S., Pala, V., Venturelli, E., Secreto, G., Barrett-Connor, E., Laughlin, G.A., Kabuto, M., Akiba, S., Stevens, R.G., Neriishi, K., Land, C.E., Cauley, J.A., Kuller, L.H., Cummings, S.R., Helzlsouer, K.J., Alberg, A.J., Bush, T.L., Comstock, G.W., Gordon, G.B., Miller, S.R., 2003. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95, 1218-1226. Kiyohara, C., 1996. Role of cytochrome P4501A1 (CYP1A1) in lung cancer sensitivity. Fukuoka Igaku Zasshi 87, 185-188. Kohno, T., Shinmura, K., Tosaka, M., Tani, M., Kim, S.R., Sugimura, H., Nohmi, T., Kasai, H., Yokota, J., 1998. Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA. Oncogene 16, 3219-3225. Kosti, O., Xu, X., Veenstra, T.D., Hsing, A.W., Chu, L.W., Goldman, L., Bebu, I., Collins, S., Dritschilo, A., Lynch, J.H., Goldman, R., 2011. Urinary estrogen metabolites and prostate cancer risk: a pilot study. Prostate 71, 507-516. Krajinovic, M., Ghadirian, P., Richer, C., Sinnett, H., Gandini, S., Perret, C., Lacroix, A., Labuda, D., Sinnett, D., 2001. Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene-environment interactions. Int J Cancer 92, 220-225. Kubo, K., Ide, H., Wallace, S.S., Kow, Y.W., 1992. A novel, sensitive, and specific assay for abasic sites, the most commonly produced DNA lesion. Biochemistry 31, 3703-3708. Lachman, H.M., Papolos, D.F., Saito, T., Yu, Y.M., Szumlanski, C.L., Weinshilboum, R.M., 1996. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 6, 243-250. Landi, M.T., Bertazzi, P.A., Shields, P.G., Clark, G., Lucier, G.W., Garte, S.J., Cosma, G., Caporaso, N.E., 1994. Association between CYP1A1 genotype, mRNA expression and enzymatic activity in humans. Pharmacogenetics 4, 242-246. Larsen, J.E., Colosimo, M.L., Yang, I.A., Bowman, R., Zimmerman, P.V., Fong, K.M., 2005. Risk of non-small cell lung cancer and the cytochrome P4501A1 Ile462Val polymorphism. Cancer Causes Control 16, 579-585. Lee, S.M., Park, J.H., Park, H.J., 2008. Breast cancer risk factors in Korean women: a literature review. Int Nurs Rev 55, 355-359. Li, D.N., Seidel, A., Pritchard, M.P., Wolf, C.R., Friedberg, T., 2000. Polymorphisms in P450 CYP1B1 affect the conversion of estradiol to the potentially carcinogenic metabolite 4-hydroxyestradiol. Pharmacogenetics and Genomics 10, 343-353. Liehr, J.G., 2000. Is estradiol a genotoxic mutagenic carcinogen. Liehr, J.G., Ricci, M.J., 1996. 4-Hydroxylation of estrogens as marker of human mammary tumors. Lin, C.Y., Strom, A., Vega, V.B., Kong, S.L., Yeo, A.L., Thomsen, J.S., Chan, W.C., Doray, B., Bangarusamy, D.K., Ramasamy, A., Vergara, L.A., Tang, S., Chong, A., Bajic, V.B., Miller, L.D., Gustafsson, J.A., Liu, E.T., 2004. Discovery of estrogen receptor alpha target genes and response elements in breast tumor cells. Genome Biol 5, R66. Lin, P.H., Nakamura, J., Yamaguchi, S., Asakura, S., Swenberg, J.A., 2003. Aldehydic DNA lesions induced by catechol estrogens in calf thymus DNA. Carcinogenesis 24, 1133-1141. Ma, Q., Lu, A.Y.H., 2007. CYP1A Induction and Human Risk Assessment: An Evolving Tale of in Vitro and in Vivo Studies. Drug Metabolism and Disposition 35, 1009-1016. Madigan, M.T., Martinko, J.M., 2006. Biology of microorganisms. Mitrunen, K., Hirvonen, A., 2003. Molecular epidemiology of sporadic breast cancer. The role of polymorphic genes involved in oestrogen biosynthesis and metabolism. Mutat Res 544, 9-41. Miyoshi, Y., Noguchi, S., 2003. Polymorphisms of estrogen synthesizing and metabolizing genes and breast cancer risk in Japanese women. Biomedecine & Pharmacotherapy 57, 471-481. Miyoshi, Y., Takahashi, Y., Egawa, C., Noguchi, S., 2002. Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women. Breast J 8, 209-215. Nakamura, J., Swenberg, J.A., 1999. Endogenous apurinic/apyrimidinic sites in genomic DNA of mammalian tissues. Cancer Res 59, 2522-2526. Nakamura, J., Walker, V.E., Upton, P.B., Chiang, S.Y., Kow, Y.W., Swenberg, J.A., 1998. Highly sensitive apurinic/apyrimidinic site assay can detect spontaneous and chemically induced depurination under physiological conditions. Cancer Res 58, 222-225. Pasqualini, J.R., Chetrite, G., Blacker, C., Feinstein, M.C., Delalonde, L., Talbi, M., Maloche, C., 1996. Concentrations of estrone, estradiol, and estrone sulfate and evaluation of sulfatase and aromatase activities in pre- and postmenopausal breast cancer patients. J Clin Endocrinol Metab 81, 1460-1464. Peng, K.W., Wang, H., Qin, Z., Wijewickrama, G.T., Lu, M., Wang, Z., Bolton, J.L., Thatcher, G.R., 2009. Selective estrogen receptor modulator delivery of quinone warheads to DNA triggering apoptosis in breast cancer cells. ACS Chem Biol 4, 1039-1049. Rogan, E.G., Badawi, A.F., Devanesan, P.D., Meza, J.L., Edney, J.A., West, W.W., Higginbotham, S.M., Cavalieri, E.L., 2003. Relative imbalances in estrogen metabolism and conjugation in breast tissue of women with carcinoma: potential biomarkers of susceptibility to cancer. Rylander-Rudqvist, T., Wedren, S., Granath, F., Humphreys, K., Ahlberg, S., Weiderpass, E., Oscarson, M., Ingelman-Sundberg, M., Persson, I., 2003. Cytochrome P450 1B1 gene polymorphisms and postmenopausal breast cancer risk. Carcinogenesis 24, 1533-1539. Schernhammer, E.S., Tworoger, S.S., Eliassen, A.H., Missmer, S.A., Holly, J.M., Pollak, M.N., Hankinson, S.E., 2007. Body shape throughout life and correlations with IGFs and GH. Endocr Relat Cancer 14, 721-732. Shieldsbotella, J., Chetrite, G., Meschi, S., Pasqualini, J., 2005. Effect of nomegestrol acetate on estrogen biosynthesis and transformation in MCF-7 and T47-D breast cancer cells. The Journal of Steroid Biochemistry and Molecular Biology 93, 1-13. Shimada, T., Oda, Y., Gillam, E.M., Guengerich, F.P., Inoue, K., 2001. Metabolic activation of polycyclic aromatic hydrocarbons and other procarcinogens by cytochromes P450 1A1 and P450 1B1 allelic variants and other human cytochromes P450 in Salmonella typhimurium NM2009. Drug Metab Dispos 29, 1176-1182. Shin, A., Kang, D., Choi, J.Y., Lee, K.M., Park, S.K., Noh, D.Y., Ahn, S.H., Yoo, K.Y., 2007. Cytochrome P450 1A1 (CYP1A1) polymorphisms and breast cancer risk in Korean women. Exp Mol Med 39, 361-366. Smith, T.R., Levine, E.A., Freimanis, R.I., Akman, S.A., Allen, G.O., Hoang, K.N., Liu-Mares, W., Hu, J.J., 2008. Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis 29, 2132-2138. Smith, T.R., Miller, M.S., Lohman, K.K., Case, L.D., Hu, J.J., 2003. DNA damage and breast cancer risk. Carcinogenesis 24, 883-889. Stanczyk, F.Z., Jurow, J., Hsing, A.W., 2010. Limitations of direct immunoassays for measuring circulating estradiol levels in postmenopausal women and men in epidemiologic studies. Cancer Epidemiol Biomarkers Prev 19, 903-906. Sugimura, H., Wakai, K., Genka, K., Nagura, K., Igarashi, H., Nagayama, K., Ohkawa, A., Baba, S., Morris, B.J., Tsugane, S., Ohno, Y., Gao, C., Li, Z., Takezaki, T., Tajima, K., Iwamasa, T., 1998. Association of Ile462Val (Exon 7) polymorphism of cytochrome P450 IA1 with lung cancer in the Asian population: further evidence from a case-control study in Okinawa. Cancer Epidemiol Biomarkers Prev 7, 413-417. Suzuki, M., Mamun, M.R., Hara, K., Ozeki, T., Yamada, Y., Kadowaki, T., Honda, H., Yanagihara, Y., Ito, Y.M., Kameyama, S., Ohta, N., Hosoi, T., Arai, T., Sawabe, M., Takeuchi, T., Takahashi, S., Kitamura, T., 2005. The Val158Met polymorphism of the catechol-O-methyltransferase gene is associated with the PSA-progression-free survival in prostate cancer patients treated with estramustine phosphate. Eur Urol 48, 752-759. Sweeney, C., Baumgartner, K.B., Byers, T., Giuliano, A.R., Herrick, J.S., Murtaugh, M.A., Slattery, M.L., 2007. Reproductive history in relation to breast cancer risk among Hispanic and non-Hispanic white women. Cancer Causes & Control 19, 391-401. Swenberg, J.A., Lu, K., Moeller, B.C., Gao, L., Upton, P.B., Nakamura, J., Starr, T.B., 2011. Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment. Toxicol Sci 120 Suppl 1, S130-145. Szymczak, J., Milewicz, A., Thijssen, J.H., Blankenstein, M.A., Daroszewski, J., 1998. Concentration of sex steroids in adipose tissue after menopause. Steroids 63, 319-321. Tabor, H.K., Risch, N.J., Myers, R.M., 2002. Candidate-gene approaches for studying complex genetic traits: practical considerations. Nat Rev Genet 3, 391-397. Taioli, E., Bradlow, H.L., Garbers, S.V., Sepkovic, D.W., Osborne, M.P., Trachman, J., Ganguly, S., Garte, S.J., 1999. Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk. Cancer Detect Prev 23, 232-237. Tanaka, Y., Sasaki, M., Kaneuchi, M., Shiina, H., Igawa, M., Dahiya, R., 2002. Polymorphism of the CYP1B1 gene have higher risk for prostate cancer. Tang, Y.M., Wo, Y.Y., Stewart, J., Hawkins, A.L., Griffin, C.A., Sutter, T.R., Greenlee, W.F., 1996. Isolation and characterization of the human cytochrome P450 CYP1B1 gene. J Biol Chem 271, 28324-28330. Taylor, A.H., Al-Azzawi, F., 2000. Immunolocalisation of oestrogen receptor beta in human tissues. J Mol Endocrinol 24, 145-155. Tenhunen, J., Heikkila, P., Alanko, A., Heinonen, E., Akkila, J., Ulmanen, I., 1999. Soluble and membrane-bound catechol-O-methyltransferase in normal and malignant mammary gland. Cancer Lett 144, 75-84. Thijssen, J.H., van Landeghem, A.A., Poortman, J., 1986. Uptake and concentration of steroid hormones in mammary tissues. Ann N Y Acad Sci 464, 106-116. Tworoger, S.S., Eliassen, A.H., Missmer, S.A., Baer, H., Rich-Edwards, J., Michels, K.B., Barbieri, R.L., Dowsett, M., Hankinson, S.E., 2006. Birthweight and body size throughout life in relation to sex hormones and prolactin concentrations in premenopausal women. Cancer Epidemiol Biomarkers Prev 15, 2494-2501. Vodicka, P., Stetina, R., Polakova, V., Tulupova, E., Naccarati, A., Vodickova, L., Kumar, R., Hanova, M., Pardini, B., Slyskova, J., Musak, L., De Palma, G., Soucek, P., Hemminki, K., 2007. Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects. Carcinogenesis 28, 657-664. Watanabe, J., Shimada, T., Gillam, E.M., Ikuta, T., Suemasu, K., Higashi, Y., Gotoh, O., Kawajiri, K., 2000. Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer. Pharmacogenetics 10, 25-33. Waters, L.S., Minesinger, B.K., Wiltrout, M.E., D''Souza, S., Woodruff, R.V., Walker, G.C., 2009. Eukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance. Microbiology and Molecular Biology Reviews 73, 134-154. Wood, R.D., 1996. DNA repair in eukaryotes. Annu Rev Biochem 65, 135-167. Yager, J.D., Davidson, N.E., 2006. Estrogen Carcinogenesis in Breast Cancer. New England Journal of Medicine 354, 270-282. Yim, D.-S., Park, S.K., Yoo, K.-Y., Yoon, K.-S., Chung, H.H., Kang, H.J., Ahn, S.-H., Noh, D.-Y., Choe, K.-J., Jang, I.-J., Shin, S.-G., Strickland, P.T., Hirvonen, A., Kang, D., 2001. Relationship between the Val158Met polymorphism of catechol O-methyl transferase and breast cancer. Pharmacogenetics and Genomics 11, 279-286. Yuan, W., Xu, L., Feng, Y., Yang, Y., Chen, W., Wang, J., Pang, D., Li, D., 2010. The hOGG1 Ser326Cys polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 122, 835-842. Zheng, W., Xie, D.W., Jin, F., Cheng, J.R., Dai, Q., Wen, W.Q., Shu, X.O., Gao, Y.T., 2000. Genetic polymorphism of cytochrome P450-1B1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 9, 147-150. Zhu, B.T., Conney, A.H., 1998. Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis 19, 1-27. Ziegler, R.G., Faupel-Badger, J.M., Sue, L.Y., Fuhrman, B.J., Falk, R.T., Boyd-Morin, J., Henderson, M.K., Hoover, R.N., Veenstra, T.D., Keefer, L.K., Xu, X., 2010. A new approach to measuring estrogen exposure and metabolism in epidemiologic studies. J Steroid Biochem Mol Biol 121, 538-545. Zimarina, T.C., Kristensen, V.N., Imianitov, E.N., Bershtein, L.M., 2004. Polymorphisms of CYP1B1 and COMT in breast and endometrial cancer. Mol Biol (Mosk) 38, 386-393.
乳癌是台灣女性最普遍癌症之一,在許多流行病學研究指出雌性激素劑量累積為乳癌風險之重要因素。實驗室先前研究證實雌性激素醌類代謝物會直接造成DNA (deoxyribonucleic acid) 氧化損害而形成去鹼基核酸 (AP sites),此即為雌性激素致癌的重要起始化作用 (initiation)。本研究主要目的為探討台灣女性乳癌病患之乳癌風險因子,包括年齡、身體質量指數 (BMI) 及雌性激素代謝基因之基因多型性與去鹼基核酸背景值之相關性,此研究將以102位台灣女性乳癌病患之白血球進行分析。
研究結果顯示,乳癌病患AP sites背景值為 94.3 ± 107/106核苷酸 (平均 ± 標準偏差)。而乳癌病患之雌性激素代謝活化之對偶基因變異 (variant alleles) 頻率CYP1A1 T3801C與CYP1B1 Leu432Val分別為39.7%與7.35%。我們也發現在BMI < 27之乳癌病患其AP sites背景值較BMI ≧ 27病患為高,而此趨勢在年齡小於50歲研究族群更明顯。此外,乳癌病患CYP1A1 T3801C 不同基因型病患其AP sites背景值約略相當;但在年齡小於50歲的乳癌病患中,CYP1B1 Leu432Val Leu/Val+Val/Val基因型 (高活性) 之AP sites背景值較Leu/Leu基因型高約1.4倍。由AP site cleavage assay結果指出,乳癌病患之AP sites可能是由氧化作用引起。
綜合上述研究結果可發現,乳癌風險因子包括年齡及BMI與乳癌病患之AP sites背景值呈負相關;而CYP1B1 Leu432Val對偶基因之變異型與乳癌病患AP sites背景值呈正相關。

Breast cancer is one of the most prevalent cancer among women in Taiwan. Epidemiological studies suggest that cumulative estrogen dose is a key determinant of breast cancer risks. Laboratory research provides evidence that estrogen quinone-derived direct and oxidative DNA (deoxyribonucleic acid) damage and the subsequent formation of abasic sites (AP sites) play an important role in the initiation of estrogen carcinogenesis. The objective of this research was to investigate association of the risk factors of breast cancer, including age, body mass index (BMI), and polymorphism of genes responsible for estrogen disposition, with the background levels of AP sites in white blood cells derived from 102 female breast cancer patients in Taiwan.
Results indicated that the background levels of AP sites (mean ± SD) in breast cancer patients was 94.3 ± 107 per 106 nucleotides. The frequencies of variant alleles of CYP1A1 T3801C and CYP1B1 Leu432Val were estimated to be 39.7% and 7.35%, respectively. We noticed that the background levels of AP sites in breast cancer patients with BMI < 27 were greater than those with BMI ≧ 27, and the tendency was more obvious in subjects under 50 years of age. Relatively similar levels of AP sites were detected in subjects with SNP of CYP1A1 T3801C T/T genotype when compared to those with T/C and C/C genotype. A 1.4-fold increase in the number of AP sites was detected in patients (age < 50) with CYP1B1 Leu432Val Leu/Val+Val/Val genotype (high-activity) when compared to those with Leu/Leu genotype. Additionally, results from the AP site cleavage assay indicated that the AP sites detected in breast cancer patients were likely to derive from oxidative events. The background levels of AP sites had no significant difference distinguished by age or BMI in breast cancer patients who received chemotherapy.
In conclusions, the risk factors of developing breast cancer, including age, BMI, and variant allele of CYP1A1 T3801C, were negatively correlated with the background levels of AP sites whereas variant allele of CYP1B1 Leu432Val were positively correlated with the background levels of AP sites in breast cancer patients.
其他識別: U0005-1908201114473200
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