Estrogen-Metabolizing Gene Polymorphisms, Genetic Susceptibility, and Pharmacogenomics

  • Johannes C. Huber
  • Eva-Katrin Tempfer-Bentz
  • Johannes Ott
  • Clemens B. Tempfer
Part of the Cancer Genetics book series (CANGENETICS)


A unique feature of steroids is their capacity for metamorphosis. Steroid hormones can be transformed into various metabolites exerting diverse effects. Converted steroids can be inactive, result in excretion of the steroid, occupy different receptors, and sometimes even show antagonistic effects to the precursor. This phenomenon is well documented for progesterone, androgens, and estrogen.


Breast Cancer Breast Cancer Risk Lung Cancer Risk Increase Breast Cancer Risk Estrogen Metabolite 


  1. 1.
    Jefcoate CR, Jefcoate CR, Liehr JG, Santen RJ, et al. Tissue-specific synthesis and oxidative metabolism of estrogens. In: Estrogens as endogenous carcinogens in the breast and prostate. Journal of the National Cancer Institute monograph. No. 27. Bethesda, MD: National Cancer Institute, 2000;95–112.Google Scholar
  2. 2.
    Liehr JG. Is estradiol a genotoxic mutagenic carcinogen? Endocr Rev. 2000;21:40–54.PubMedGoogle Scholar
  3. 3.
    Hayes CL, Spink DC, Spink BC, Cao JQ, Walker NJ, Sutter TR. 17 Beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proc Natl Acad Sci U S A. 1996;93:9776–81.PubMedGoogle Scholar
  4. 4.
    Williams JA, Phillips DH. Mammary expression of xenobiotic metabolizing enzymes and their potential role in breast cancer. Cancer Res. 2000;60:4667–77.PubMedGoogle Scholar
  5. 5.
    Yue W, Santen RJ, Wang JP, et al. Genotoxic metabolites of estradiol in breast: potential mechanism of estradiol induced carcinogenesis. J Steroid Biochem Mol Biol. 2003;86:477–86.PubMedGoogle Scholar
  6. 6.
    Cavalieri E, Frenkel K, Liehr JG, Rogan E, Roy D. Estrogens as endogenous genotoxic agents – DNA adducts and mutations. In: Estrogens as endogenous carcinogens in the breast and prostate. Journal of the National Cancer Institute monograph. No. 27. Bethesda, MD: National Cancer Institute, 2000;75–93.Google Scholar
  7. 7.
    Devanesan P, Todorovic R, Zhao J, Gross ML, Rogan EG, Cavalieri EL. Catechol estrogen conjugates and DNA adducts in the kidney of male Syrian golden hamsters treated with 4 hydroxyestradiol: potential biomarkers for estrogen-initiated cancer. Carcinogenesis. 2001;22:489–97.PubMedGoogle Scholar
  8. 8.
    Cavalieri EL, Kumar S, Todorovic R, Higginbotham S, Badawi AF, Rogan EG. Imbalance of estrogen homeostasis in kidney and liver of hamsters treated with estradiol: implications for estrogen-induced initiation of renal tumors. Chem Res Toxicol. 2001;14:1041–50.PubMedGoogle Scholar
  9. 9.
    Chakravarti D, Mailander PC, Li KM, et al. Evidence that a burst of DNA depurination in SENCAR mouse skin induces error-prone repair and forms mutations in the H-ras gene. Oncogene. 2001;20:7945–53.PubMedGoogle Scholar
  10. 10.
    van Landeghem AA, Poortman J, Nabuurs M, Thijssen JH. Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue. Cancer Res. 1985;45:2900–6.PubMedGoogle Scholar
  11. 11.
    Mitrunen K, Hirvonen A. Molecular epidemiology of sporadic breast cancer: the role of polymorphic genes involved in oestrogen biosynthesis and metabolism. Mutat Res. 2003;544:9–41.PubMedGoogle Scholar
  12. 12.
    Ritchie MD, Hahn LW, Roodi N, et al. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet. 2001;69:138–47.PubMedGoogle Scholar
  13. 13.
    Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT. Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003;144(8):3382–98.PubMedGoogle Scholar
  14. 14.
    Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. 2-hydroxyestrone: the ‘good’ estrogen. J Endocrinol. 1996;150 Suppl:S259–65.Google Scholar
  15. 15.
    Firozi PF, Bondy ML, Sahin AA, Chang P, Lukmanji F, Singletary ES, Hassan MM, Li D. Aromatic DNA adducts and polymorphisms of CYP1A1, NAT2, and GSTM1 in breast cancer. Carcinogenesis. 2002;23(2):301–6.PubMedGoogle Scholar
  16. 16.
    McManus ME, Burgess WM, Veronese ME, Huggett A, Quattrochi LC, Tukey RH. Metabolism of 2-acetylaminofluorene and benzo(a)pyrene and activation of food-derived heterocyclic amine mutagens by human cytochromes P-450. Cancer Res. 1990;50(11):3367–76.PubMedGoogle Scholar
  17. 17.
    Shen Y, Li DK, Wu J, Zhang Z, Gao E. Joint effects of the CYP1A1 MspI, ERalpha PvuII, and ERalpha XbaI polymorphisms on the risk of breast cancer: results from a population-based case–control study in Shanghai, China. Cancer Epidemiol Biomarkers Prev. 2006;15(2):342–7.PubMedGoogle Scholar
  18. 18.
    Spurr NK, Gough AC, Stevenson K, Wolf CR. Msp-1 polymorphism detected with a cDNA probe for the P-450 I family on chromosome 15. Nucleic Acids Res. 1987;15(14):5901.PubMedGoogle Scholar
  19. 19.
    Hayashi SI, Watanabe J, Nakachi K, Kawajiri K. PCR detection of an A/G polymorphism within exon 7 of the CYP1A1 gene. Nucleic Acids Res. 1991;19(17):4797.PubMedGoogle Scholar
  20. 20.
    Crofts F, Cosma GN, Currie D, Taioli E, Toniolo P, Garte SJ. A novel CYP1A1 gene polymorphism in African-Americans. Carcinogenesis. 1993;14(9):1729–31.PubMedGoogle Scholar
  21. 21.
    Cascorbi I, Brockmoller J, Roots I. A C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkages, and impact on lung cancer susceptibility. Cancer Res. 1996;56(21):4965–9.PubMedGoogle Scholar
  22. 22.
    Kawajiri K. CYP1A1. IARC Sci Publ. 1999;(148):159–72.Google Scholar
  23. 23.
    Cosma G, Crofts F, Taioli E, Toniolo P, Garte S. Relationship between genotype and function of the human CYP1A1 gene. J Toxicol Environ Health. 1993;40(2–3):309–16.PubMedGoogle Scholar
  24. 24.
    Kiyohara C, Hirohata T, Inutsuka S. The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene. Jpn J Cancer Res. 1996;87(1):18–24.PubMedGoogle Scholar
  25. 25.
    Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol Biomarkers Prev. 2000;9(1):3–28.PubMedGoogle Scholar
  26. 26.
    Masson LF, Sharp L, Cotton SC, Little J. Cytochrome P-450 1A1 gene polymorphisms and risk of breast cancer: a HuGE review. Am J Epidemiol. 2005;161(10):901–15.PubMedGoogle Scholar
  27. 27.
    Ishibe N, Hankinson SE, Colditz GA, Spiegelman D, Willett WC, Speizer FE, Kelsey KT, Hunter DJ. Cigarette smoking, cytochrome P450 1A1 polymorphisms, and breast cancer risk in the Nurses’ Health Study. Cancer Res. 1998;58(4):667–71.PubMedGoogle Scholar
  28. 28.
    Michnovicz JJ, Adlercreutz H, Bradlow HL. Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst. 1997;89(10):718–23.PubMedGoogle Scholar
  29. 29.
    Kisselev P, Schunck WH, Roots I, Schwarz D. Association of CYP1A1 polymorphisms with differential metabolic activation of 17beta-estradiol and estrone. Cancer Res. 2005;65(7):2972–8.PubMedGoogle Scholar
  30. 30.
    Garte SJ, Trachman J, Crofts F, Toniolo P, Buxbaum J, Bayo S, Taioli E. Distribution of composite CYP1A1 genotypes in Africans, African-Americans and Caucasians. Hum Hered. 1996;46:121–127.Google Scholar
  31. 31.
    Chen C, Huang Y, Li Y, Mao Y, Xie Y. Cytochrome P450 1A1 (CYP1A1) T3801C and A2455G polymorphisms in breast cancer risk: a meta-analysis. J Hum Genet. 2007;52(5):423–35. Epub 2007 Apr 11PubMedGoogle Scholar
  32. 32.
    Terry KL, Titus-Ernstoff L, Garner EO, Vitonis AF, Cramer DW. Interaction between CYP1A1 polymorphic variants and dietary exposures influencing ovarian cancer risk. Cancer Epidemiol Biomarkers Prev. 2003;12(3):187–90.PubMedGoogle Scholar
  33. 33.
    Vineis P, Veglia F, Benhamou S, et al. CYP1A1 T3801C polymorphism and lung cancer: a pooled analysis of 2451 cases and 3358 controls. Int J Cancer. 2003;104:650–7.PubMedGoogle Scholar
  34. 34.
    Le Marchand L, Guo C, Benhamou S, et al. Pooled analysis of the CYP1A1 exon 7 polymorphism and lung cancer (United States). Cancer Causes Control. 2003;14:339–46.PubMedGoogle Scholar
  35. 35.
    Taioli E, Gaspari L, Benhamou S, et al. Polymorphisms in CYP1A1, GSTM1, GSTT1 and lung cancer below the age of 45 years. Int J Epidemiol. 2003;32:60–3.PubMedGoogle Scholar
  36. 36.
    Hung RJ, Boffetta P, Brockmoller J, et al. CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: a pooled analysis. Carcinogenesis. 2003;24:875–82.PubMedGoogle Scholar
  37. 37.
    Kawajiri K, Nakachi K, Imai K, Watanabe J, Hayashi S. The CYP1A1 gene and cancer susceptibility. Crit Rev Oncol Hematol. 1993;14(1):77–87.PubMedGoogle Scholar
  38. 38.
    Kawajiri K, Nakachi K, Imai K, Yoshii A, Shinoda N, Watanabe J. Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P450IA1 gene. FEBS Lett. 1990;263(1):131–3.PubMedGoogle Scholar
  39. 39.
    Houlston RS. CYP1A1 polymorphisms and lung cancer risk: a meta-analysis. Pharmacogenetics. 2000;10(2):105–14.PubMedGoogle Scholar
  40. 40.
    Kawajiri K, et al. Metabolic polymorphisms and susceptibility to cancer. IARC Sci Publ. 1999:148:159–172.PubMedGoogle Scholar
  41. 41.
    Le Marchand L, Donlon T, Kolonel LN, Henderson BE, Wilkens LR. Estrogen metabolism-related genes and breast cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev. 2005;14(8):1998–2003.PubMedGoogle Scholar
  42. 42.
    Vineis P, Veglia F, Anttila S, Benhamou S, Clapper ML, Dolzan V, Ryberg D, Hirvonen A, Kremers P, Le Marchand L, Pastorelli R, Rannug A, Romkes M, Schoket B, Strange RC, Garte S, Taioli E. CYP1A1, GSTM1 and GSTT1 polymorphisms and lung cancer: a pooled analysis of gene–gene interactions. Biomarkers. 2004;9(3):298–305.PubMedGoogle Scholar
  43. 43.
    Wang X, Zuckerman B, Pearson C, Kaufman G, Chen C, Wang G, Niu T, Wise PH, Bauchner H, Xu X. Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. JAMA. 2002;287(2):195–202.PubMedGoogle Scholar
  44. 44.
    Roth MJ, Abnet CC, Johnson LL, Mark SD, Dong ZW, Taylor PR, Dawsey SM, Qiao YL. Polymorphic variation of Cyp1A1 is associated with the risk of gastric cardia cancer: a prospective case–cohort study of cytochrome P-450 1A1 and GST enzymes. Cancer Causes Control. 2004;15(10):1077–83.PubMedGoogle Scholar
  45. 45.
    Abbas A, Delvinquiere K, Lechevrel M, Lebailly P, Gauduchon P, Launoy G, Sichel F. GSTM1, GSTT1, GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population: different pattern of squamous cell carcinoma and adenocarcinoma. World J Gastroenterol. 2004;10(23):3389–93.PubMedGoogle Scholar
  46. 46.
    Slattery ML, Samowtiz W, Ma K, Murtaugh M, Sweeney C, Levin TR, Neuhausen S. CYP1A1, cigarette smoking, and colon and rectal cancer. Am J Epidemiol. 2004;160(9):842–52.PubMedGoogle Scholar
  47. 47.
    Wang XL, Greco M, Sim AS, Duarte N, Wang J, Wilcken DE. Effect of CYP1A1 MspI polymorphism on cigarette smoking related coronary artery disease and diabetes. Atherosclerosis. 2002;162(2):391–7.PubMedGoogle Scholar
  48. 48.
    Fritsche E, Schuppe HC, Döhr O, Ruzicka T, Gleichmann E, Abel J. Increased frequencies of cytochrome P4501A1 polymorphisms in infertile men. Andrologia. 1998;30(3):125–8.PubMedGoogle Scholar
  49. 49.
    von Schmiedeberg S, Fritsche E, Rönnau AC, Specker C, Golka K, Richter-Hintz D, Schuppe HC, Lehmann P, Ruzicka T, Esser C, Abel J, Gleichmann E. Polymorphisms of the xenobiotic-metabolizing enzymes CYP1A1 and NAT-2 in systemic sclerosis and lupus erythematosus. Adv Exp Med Biol. 1999;455:147–52.Google Scholar
  50. 50.
    Gardlo K, Selimovic D, Bolsen K, Ruzicka T, Abel J, Fritsch C. Cytochrome p450A1 polymorphisms in a Caucasian population with porphyria cutanea tarda. Exp Dermatol. 2003;12(6):843–8.PubMedGoogle Scholar
  51. 51.
    Richter-Hintz D, Their R, Steinwachs S, Kronenberg S, Fritsche E, Sachs B, Wulferink M, Tonn T, Esser C. Allelic variants of drug metabolizing enzymes as risk factors in psoriasis. J Invest Dermatol. 2003;120(5):765–70.PubMedGoogle Scholar
  52. 52.
    Yen JH, Tsai WC, Chen CJ, Lin CH, Ou TT, Hu CJ, Liu HW. Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in ankylosing spondylitis. Immunol Lett. 2003;88(2):113–6.PubMedGoogle Scholar
  53. 53.
    Yen JH, Chen CJ, Tsai WC, Lin CH, Ou TT, Hu CJ, Liu HW. Manganese superoxide dismutase and cytochrome P450 1A1 genes polymorphisms in rheumatoid arthritis in Taiwan. Hum Immunol. 2003;64(3):366–73.PubMedGoogle Scholar
  54. 54.
    Arvanitis DA, Koumantakis GE, Goumenou AG, Matalliotakis IM, Koumantakis EE, Spandidos DA. CYP1A1, CYP19, and GSTM1 polymorphisms increase the risk of endometriosis. Fertil Steril. 2003;79 Suppl 1:702–9.PubMedGoogle Scholar
  55. 55.
    Hadfield RM, Manek S, Weeks DE, Mardon HJ, Barlow DH, Kennedy SH, OXEGENE Collaborative Group. Linkage and association studies of the relationship between endometriosis and genes encoding the detoxification enzymes GSTM1, GSTT1 and CYP1A1. Mol Hum Reprod. 2001;7(11):1073–8.PubMedGoogle Scholar
  56. 56.
    Iizuka S, Kosugi Y, Isaka K, et al. Could polymorphisms of N-acetyltransferase 2 (NAT2), glutathione S-transferase M1 (GSTM1), and cytochrome P450 (CYP1A1) be responsible for genetic predisposition to endometriosis among Japanese? Zasshi Tokyo Ika Daigaku. 2003;61:59–66.Google Scholar
  57. 57.
    Nicholl DJ, Bennett P, Hiller L, Bonifati V, Vanacore N, Fabbrini G, Marconi R, Colosimo C, Lamberti P, Stocchi F, Bonuccelli U, Vieregge P, Ramsden DB, Meco G, Williams AC. A study of five candidate genes in Parkinson’s disease and related neurodegenerative disorders. European Study Group on Atypical Parkinsonism. Neurology. 1999;53(7):1415–21.PubMedGoogle Scholar
  58. 58.
    Chan DK, Mellick GD, Buchanan DD, Hung WT, Ng PW, Woo J, Kay R. Lack of association between CYP1A1 polymorphism and Parkinson’s disease in a Chinese population. J Neural Transm. 2002;109(1):35–9.PubMedGoogle Scholar
  59. 59.
    Takakubo F, Yamamoto M, Ogawa N, Yamashita Y, Mizuno Y, Kondo I. Genetic association between cytochrome P450IA1 gene and susceptibility to Parkinson’s disease. J Neural Transm. 1996;103(7):843–9.PubMedGoogle Scholar
  60. 60.
    Kurth MC, Kurth JH. Variant cytochrome P450 CYP2D6 allelic frequencies in Parkinson’s disease. Am J Med Genet. 1993;48(3):166–8.PubMedGoogle Scholar
  61. 61.
    Ciolino HP, Yeh GC. Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol. Mol Pharmacol. 1999;56(4):760–7.PubMedGoogle Scholar
  62. 62.
    Muskhelishvili L, Thompson PA, Kusewitt DF, Wang C, Kadlubar FF. In situ hybridization and immunohistochemical analysis of cytochrome P450 1B1 expression in human normal tissues. J Histochem Cytochem. 2001;49:229–36.PubMedGoogle Scholar
  63. 63.
    Rochat B, Morsman JM, Murray GI, Figg WD, McLeod HL. Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation? J Pharmacol Exp Ther. 2001;296:537–41.PubMedGoogle Scholar
  64. 64.
    Wen W. Expression of cytochrome P450 1B1 and catechol-O-methyltransferase in breast tissue and their associations with breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2007;16(5):917–20.PubMedGoogle Scholar
  65. 65.
    McKay JA, Melvin WT, Ah-See AK, et al. Expression of cytochrome P450 CYP1B1 in breast cancer. FEBS Lett. 1995;374:270–2.PubMedGoogle Scholar
  66. 66.
    Hatanaka N, Yamazaki H, Oda Y, Guengerich FP, Nakajima M, Yokoi T. Metabolic activation of carcinogenic 1-nitropyrene by human cytochrome P450 1B1 in Salmonella typhimurium strain expressing an O-acetyltransferase in SOS/umu assay. Mutat Res. 2001;497:223–33.PubMedGoogle Scholar
  67. 67.
    Listgarten J, Damaraju S, Poulin B, et al. Predictive models for breast cancer susceptibility from multiple single nucleotide polymorphisms. Clin Cancer Res. 2004;10:2725–37.PubMedGoogle Scholar
  68. 68.
    Shimada T, Hayes CL, Yamazaki H, et al. Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1. Cancer Res. 1996;56:2979–84.PubMedGoogle Scholar
  69. 69.
    Tanaka Y, Sasaki M, Kaneuchi M, Shiina H, Igawa M, Dahiya R. Polymorphisms of the CYP1B1 gene have higher risk for prostate cancer. Biochem Biophys Res Commun. 2002;296:820–6.PubMedGoogle Scholar
  70. 70.
    Stoilov I, Akarsu AN, Alozie I, et al. Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p21 results from mutations disrupting either the hinge region or the conserved core structures of cytochrome P4501B1. Am J Hum Genet. 1998;62:573–84.PubMedGoogle Scholar
  71. 71.
    Cuthill S, Poellinger L, Gustafsson JA. The receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse hepatoma cell line Hepa 1c1c7. A comparison with the glucocorticoid receptor and the mouse and rat hepatic dioxin receptors. J Biol Chem. 1987;262:3477–81.PubMedGoogle Scholar
  72. 72.
    Widschwendter M, Siegmund KD, Muller HM, et al. Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifen. Cancer Res. 2004;64:3807–13.PubMedGoogle Scholar
  73. 73.
    Tokizane T, Shiina H, Igawa M, et al. Cytochrome P450 1B1 is overexpressed and regulated by hypomethylation in prostate cancer. Clin Cancer Res. 2005;11:5793–801.PubMedGoogle Scholar
  74. 74.
    Han W, Kang D, Park IA, et al. Associations between breast cancer susceptibility gene polymorphisms and clinicopathological features. Clin Cancer Res. 2004;10:124–30.PubMedGoogle Scholar
  75. 75.
    Shimada T, Watanabe J, Kawajiri K, et al. Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis. 1999;20:1607–13.PubMedGoogle Scholar
  76. 76.
    Hanna IH, Dawling S, Roodi N, Guengerich FP, Parl FF. Cytochrome P450 1B1 (CYP1B1) pharmacogenetics: association of polymorphisms with functional differences in estrogen hydroxylation activity. Cancer Res. 2000;60:3440–4.PubMedGoogle Scholar
  77. 77.
    Li DN, Seidel A, Pritchard MP, Wolf CR, Friedberg T. Polymorphisms in P450 CYP1B1 affect the conversion of estradiol to the potentially carcinogenic metabolite 4-hydroxyestradiol. Pharmacogenetics. 2000;10:343–53.PubMedGoogle Scholar
  78. 78.
    Bailey LR, Roodi N, Dupont WD, Parl FF. Association of cytochrome P450 1B1 (CYP1B1) polymorphism with steroid receptor status in breast cancer. Cancer Res. 1998;58:5038–41.PubMedGoogle Scholar
  79. 79.
    Landi MT, Bergen AW, Baccarelli A, et al. CYP1A1 and CYP1B1 genotypes, haplotypes, and TCDD-induced gene expression in subjects from Seveso, Italy. Toxicology. 2005;207:191–202.PubMedGoogle Scholar
  80. 80.
    Poland A, Glover E, Bradfield CA. Characterization of polyclonal antibodies to the Ah receptor prepared by immunization with a synthetic peptide hapten. Mol Pharmacol. 1991;39:20–6.PubMedGoogle Scholar
  81. 81.
    Henry EC, Rucci G, Gasiewicz TA. Characterization of multiple forms of the Ah receptor: comparison of species and tissues. Biochemistry. 1989;28:6430–40.PubMedGoogle Scholar
  82. 82.
    Ikuta T, Eguchi H, Tachibana T, Yoneda Y, Kawajiri K. Nuclear localization and export signals of the human aryl hydrocarbon receptor. J Biol Chem. 1998;273:2895–904.PubMedGoogle Scholar
  83. 83.
    Prokipcak RD, Okey AB. Physicochemical characterization of the nuclear form of Ah receptor from mouse hepatoma cells exposed in culture to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch Biochem Biophys. 1988;267:811–28.PubMedGoogle Scholar
  84. 84.
    Paracchini V, Raimondi S, Gram IT, Kang D, Kocabas NA, Kristensen VN, Li D, Parl FF, Rylander-Rudqvist T, Soucek P, Zheng W, Wedren S, Taioli E. Meta- and pooled analyses of the cytochrome P-450 1B1 Val432Leu polymorphism and breast cancer: a HuGE-GSEC review. Am J Epidemiol. 2007;165(2):115–25. Epub 2006 Oct 19.PubMedGoogle Scholar
  85. 85.
    Saintot M, Malaveille C, Hautefeuille A, Gerber M. Interactions between genetic polymorphism of cytochrome P450-1B1, sulfotransferase 1A1, catechol-O-methyltransferase and tobacco exposure in breast cancer risk. Int J Cancer. 2003;107:652–7.PubMedGoogle Scholar
  86. 86.
    Zheng W, Xie DW, Jin F, Cheng JR, Dai Q, Wen WQ, Shu XO, Gao YT. Genetic polymorphism of cytochrome P450-1B1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2000;9:147–150.PubMedGoogle Scholar
  87. 87.
    Kocabas NA, Sardas S, Cholerton S, Daly AK, Karakaya AE. Cytochrome P450 CYP1B1 and catechol O-methyltransferase (COMT) genetic polymorphisms and breast cancer susceptibility in a Turkish population. Arch Toxicol. 2002;76:643–9.PubMedGoogle Scholar
  88. 88.
    Cook L. Hormones, genes, and cancer. New York: Oxford University Press, 2003;371–9.Google Scholar
  89. 89.
    Rylander-Rudqvist T, Wedren S, Granath F, Humphreys K, Ahlberg S, Weiderpass E, Oscarson M, Ingelman-Sundberg M, Persson I. Cytochrome P450 1B1 gene polymorphisms and postmenopausal breast cancer risk. Carcinogenesis. 24(9):1533–9. Epub 2003 Jul 4.PubMedGoogle Scholar
  90. 90.
    Justenhoven C, Pierl CB, Haas S, Fischer HP, Baisch C, Hamann U, Harth V, Pesch B, Brüning T, Vollmert C, Illig T, Dippon J, Ko YD, Brauch H. The CYP1B1_1358_GG genotype is associated with estrogen receptor-negative breast cancer. Breast Cancer Res Treat. 2007 Oct 6.Google Scholar
  91. 91.
    Liehr JG, Ricci MJ, Jefcoate CR, Hannigan EV, Hokanson JA, Zhu BT. 4-Hydroxylation of estradiol by human uterine myometrium and myoma microsomes: implications for the mechanism of uterine tumorigenesis. Proc Natl Acad Sci U S A. 1995;92:9220–4.PubMedGoogle Scholar
  92. 92.
    Newbold RR, Liehr JG. Induction of uterine adenocarcinoma in CD-1 mice by catechol estrogens. Cancer Res. 2000;60:235–7.PubMedGoogle Scholar
  93. 93.
    Raftogianis R, Creveling C, Weinshilboum R, Weisz J. Estrogen metabolism by conjugation. J Natl Cancer Inst Monogr. 2000;27:113–24.PubMedGoogle Scholar
  94. 94.
    Doostdar H, Burke MD, Mayer RT. Bioflavonoids: selective substrates and inhibitors for cytochrome P450 CYP1A and CYP1B1. Toxicology. 2000;144(1–3):31–8.PubMedGoogle Scholar
  95. 95.
    Wen X, Walle T. Preferential induction of CYP1B1 by benzo[a]pyrene in human oral epithelial cells: impact on DNA adduct formation and prevention by polyphenols. Carcinogenesis. 2005;26(10):1774–81. Epub 2005 May 19.PubMedGoogle Scholar
  96. 96.
    Sovak M. Grape extract, resveratrol, and its analogs: a review. J Med Food. 2001;4(2):93–105.PubMedGoogle Scholar
  97. 97.
    McFadyen MC, Melvin WT, Murray GI. Cytochrome P450 enzymes: novel options for cancer therapeutics. Mol Cancer Ther. 2004;3(3):363–71.PubMedGoogle Scholar
  98. 98.
    Mammen JS, Kleiner HE, DiGiovanni J, Sutter TR, Strickland PT. Coumarins are competitive inhibitors of cytochrome P450 1B1, with equal potency for allelic variants. Pharmacogenet Genomics. 2005;15(3):183–8.PubMedGoogle Scholar
  99. 99.
    Anstead GM, Carlson KE, Katzenellenbogen JA. The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids. 1997;62:268–303.PubMedGoogle Scholar
  100. 100.
    Schutze N, Vollmer G, Tiemann I, Geiger M, Knuppen R. Catecholestrogens are MCF-7 cell estrogen receptor agonists. J Steroid Biochem Mol Biol. 1993;46:781–9.PubMedGoogle Scholar
  101. 101.
    Schutze N, Vollmer G, Knuppen R. Catecholestrogens are agonists of estrogen receptor dependent gene expression in MCF-7 cells. J Steroid Biochem Mol Biol. 1994;48:453–61.PubMedGoogle Scholar
  102. 102.
    Hoogenboom LAP, de Haan L, Hooijerink D, Bor G, Murk AJ, Brouwer A. Estrogenic activity of estradiol and its metabolites in the ER-CALUX assay with human T47D breast cells. APMIS. 2001;109:101–7.PubMedGoogle Scholar
  103. 103.
    Lavigne JA, Helzlsouer KJ, Huang HY, Strickland PT, Bell DA, Selmin O, Watson MA, Hoffman S, Comstock GW, Yager JD. An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer. Cancer Res. 1997;57(24):5493–7.PubMedGoogle Scholar
  104. 104.
    Tworoger SS, Chubak J, Aiello EJ, Ulrich CM, Atkinson C, Potter JD, Yasui Y, Stapleton PL, Lampe JW, Farin FM, Stanczyk FZ, McTiernan A. Association of CYP17, CYP19, CYP1B1, and COMT polymorphisms with serum and urinary sex hormone concentrations in postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2004;13(1):94–101.PubMedGoogle Scholar
  105. 105.
    Sazci A, Ergul E, Utkan NZ, Canturk NZ, Kaya G. Catechol-O-methyltransferase Val 108/158 Met polymorphism in premenopausal breast cancer patients. Toxicology. 2004;204(2–3):197–202.PubMedGoogle Scholar
  106. 106.
    Gaudet MM, Bensen JT, Schroeder J, Olshan AF, Terry MB, Eng SM, Teitelbaum SL, Britton JA, Lehman TA, Neugut AI, Ambrosone CB, Santella RM, Gammon MD. Catechol-O-methyltransferase haplotypes and breast cancer among women on Long Island, New York. Breast Cancer Res Treat. 2006;99(2):235–40. Epub 2006 Apr 5.PubMedGoogle Scholar
  107. 107.
    Goodman JE, Lavigne JA, Wu K, Helzlsouer KJ, Strickland PT, Selhub J, Yager JD. COMT genotype, micronutrients in the folate metabolic pathway and breast cancer risk. Carcinogenesis. 2001;22(10):1661–5.PubMedGoogle Scholar
  108. 108.
    Hong CC, Thompson HJ, Jiang C, Hammond GL, Tritchler D, Yaffe M, Boyd NF. Val158Met polymorphism in catechol-O-methyltransferase gene associated with risk factors for breast cancer. Cancer Epidemiol Biomarkers Prev. 2003;12(9):838–47.PubMedGoogle Scholar
  109. 109.
    Huang P, Feng L, Oldham EA, Keating MJ, Plunkett W. Superoxide dismutase as a target for the selective killing of cancer cells. Nature. 2000;407(6802):390–5.PubMedGoogle Scholar
  110. 110.
    Nagai M, Conney AH, Zhu BT. Strong inhibitory effects of common tea catechins and bioflavonoids on the O-methylation of catechol estrogens catalyzed by human liver cytosolic catechol-O-methyltransferase. Drug Metab Dispos. 2004;32(5):497–504.PubMedGoogle Scholar
  111. 111.
    Gorai I, Tanaka K, Inada M, Morinaga H, Uchiyama Y, Kikuchi R, Chaki O, Hirahara F. Estrogen-metabolizing gene polymorphisms, but not estrogen receptor-alpha gene polymorphisms, are associated with the onset of menarche in healthy postmenopausal Japanese women. J Clin Endocrinol Metab. 2003;88(2):799–803.PubMedGoogle Scholar
  112. 112.
    Zhu BT, Conney AH. Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis. 1998;19(1):1–27.PubMedGoogle Scholar
  113. 113.
    Fotsis T, Zhang Y, Pepper MS, Adlercreutz H, Montesano R, Nawroth PP, Schweigerer L. The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature. 1994;368(6468):237–9.PubMedGoogle Scholar
  114. 114.
    Bu S, Blaukat A, Fu X, Heldin NE, Landström M. Mechanisms for 2-methoxyestradiol-induced apoptosis of prostate cancer cells. FEBS Lett. 2002;531(2):141–51.PubMedGoogle Scholar
  115. 115.
    Mabjeesh NJ, Post DE, Willard MT, Kaur B, Van Meir EG, Simons JW, Zhong H. Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells. Cancer Res. 2002;62(9):2478–82.PubMedGoogle Scholar
  116. 116.
    Lakhani NJ, Venitz J, Figg WD, Sparreboom A. Pharmacogenetics of estrogen metabolism and transport in relation to cancer. Curr Drug Metab. 2003;4(6):505–13.PubMedGoogle Scholar
  117. 117.
    Sasaki M, Kaneuchi M, Sakuragi N, Dahiya R. Multiple promoters of catechol-O-methyltransferase gene are selectively inactivated by CpG hypermethylation in endometrial cancer. Cancer Res. 2003;63(12):3101–6.PubMedGoogle Scholar
  118. 118.
    Wedrén S, Rudqvist TR, Granath F, Weiderpass E, Ingelman-Sundberg M, Persson I, Magnusson C. Catechol-O-methyltransferase gene polymorphism and post-menopausal breast cancer risk. Carcinogenesis. 2003;24(4):681–7.PubMedGoogle Scholar
  119. 119.
    Dubey RK, Gillespie DG, Zacharia LC, Rosselli M, Korzekwa KR, Fingerle J, Jackson EK. Methoxyestradiols mediate the antimitogenic effects of estradiol on vascular smooth muscle cells via estrogen receptor-independent mechanisms. Biochem Biophys Res Commun. 2000;278(1):27–33.PubMedGoogle Scholar
  120. 120.
    Dubey RK, Gillespie DG, Zacharia LC, Barchiesi F, Imthurn B, Jackson EK. CYP450- and COMT-derived estradiol metabolites inhibit activity of human coronary artery SMCs. Hypertension. 2003;41(3 Pt 2):807–13. Epub 2002 Dec 23.PubMedGoogle Scholar
  121. 121.
    Eriksson AL, Skrtic S, Niklason A, Hultén LM, Wiklund O, Hedner T, Ohlsson C. Association between low activity genotype of catechol-O-methyltransferase and myocardial infarction in a hypertensive population. Eur Heart J. 2004;25(5):386–91.PubMedGoogle Scholar
  122. 122.
    Gellekink H, Muntjewerff JW, Vermeulen SH, Hermus AR, Blom HJ, den Heijer M. Catechol-O-methyltransferase genotype is associated with plasma total homocysteine levels and may increase venous thrombosis risk. Thromb Haemost. 2007;98(6):1226–31.PubMedGoogle Scholar
  123. 123.
    Dubey RK, Jackson EK. Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms. Am J Physiol Renal Physiol. 2001;280(3):F365–88.PubMedGoogle Scholar
  124. 124.
    Mondschein JS, Hammond JM, Weisz J. Characteristics of estrogen-2/4-hydroxylase of porcine ovarian follicles: influence of steroidal and non-steroidal agents on the activity of the enzyme in vitro. J Steroid Biochem. 1987;26(1):121–4.PubMedGoogle Scholar
  125. 125.
    Levine RL, Chen SJ, Durand J, Chen YF, Oparil S. Medroxyprogesterone attenuates estrogen-mediated inhibition of neo-intima formation after balloon injury of the rat carotid artery. Circulation. 1996;94(9):2221–7.PubMedGoogle Scholar
  126. 126.
    Salama SA, Jamaluddin M, Kumar R, Hassan MH, Al-Hendy A. Progesterone regulates catechol-O-methyl transferase gene expression in breast cancer cells: distinct effect of progesterone receptor isoforms. J Steroid Biochem Mol Biol. 2007;107(3–5):253–61. Epub 2007 Jun 30.PubMedGoogle Scholar
  127. 127.
    Männistö PT, Kaakkola S. Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of new selective COMT inhibitors. Pharmacol Rev. 1999;51(4):593–628.PubMedGoogle Scholar
  128. 128.
    Saab PG, Matthews KA, Stoney CM, McDonald RH. Premenopausal and postmenopausal women differ in their cardiovascular and neuroendocrine responses to behavioural stressors. Psychophysiology. 1989;26(3):270–80.PubMedGoogle Scholar
  129. 129.
    Villecco AS, de Aloysio D, Radi D, Sprovieri G, Bargossi AM, Grossi G, Gueli C, Salgarello M, Cavrini G. Plasma catecholamines in pre- and postmenopausal women with mild to moderate essential hypertension. J Hum Hypertens. 1997;11(3):157–62.PubMedGoogle Scholar
  130. 130.
    Goldstein DS. Plasma catecholamines and essential hypertension: an analytical review. Hypertension. 1983;5(1):86–99.PubMedGoogle Scholar
  131. 131.
    Cohn JN, Johnson GR, Shabetai R, Loeb H, Tristani F, Rector T, Smith R, Fletcher R. Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. The V-HeFT VA Cooperative Studies Group. Circulation. 1993;87(6 Suppl):VI5–16.PubMedGoogle Scholar
  132. 132.
    Kaplan JR, Pettersson K, Manuck SB, Olsson G. Role of sympathoadrenal medullary activation in the initiation and progression of atherosclerosis. Circulation. 1991;84(6 Suppl):VI23–32.PubMedGoogle Scholar
  133. 133.
    Adamopoulos S, Piepoli M, McCance A, Bernardi L, Rocadaelli A, Ormerod O, Forfar C, Sleight P, Coats AJ. Comparison of different methods for assessing sympathovagal balance in chronic congestive heart failure secondary to coronary artery disease. Am J Cardiol. 1992;70(20):1576–82.PubMedGoogle Scholar
  134. 134.
    Tworoger SS, Chubak J, Aiello EJ, Yasui Y, Ulrich CM, Farin FM, Stapleton PL, Irwin ML, Potter JD, Schwartz RS, McTiernan A. The effect of CYP19 and COMT polymorphisms on exercise-induced fat loss in postmenopausal women. Obes Res. 2004;12(6):972–81.PubMedGoogle Scholar
  135. 135.
    Hart MN, Heistad DD, Brody MJ. Effect of chronic hypertension and sympathetic denervation on wall/lumen ratio of cerebral vessels. Hypertension. 1980;2(4):419–23.PubMedGoogle Scholar
  136. 136.
    Pauletto P, Scannapieco G, Pessina AC. Sympathetic drive and vascular damage in hypertension and atherosclerosis. Hypertension. 1991;17(4 Suppl):III75–81.PubMedGoogle Scholar
  137. 137.
    Worda C, Sator MO, Schneeberger C, Jantschev T, Ferlitsch K, Huber JC. Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women. Hum Reprod. 2003;18(2):262–6.PubMedGoogle Scholar
  138. 138.
    Dinenno FA, Jones PP, Seals DR, Tanaka H. Age-associated arterial wall thickening is related to elevations in sympathetic activity in healthy humans. Am J Physiol Heart Circ Physiol. 2000;278(4):H1205–10.PubMedGoogle Scholar
  139. 139.
    Bauch HJ, Grünwald J, Vischer P, Gerlach U, Hauss WH. A possible role of catecholamines in atherogenesis and subsequent complications of atherosclerosis. Exp Pathol. 1987;31(4):193–204.PubMedGoogle Scholar
  140. 140.
    Zacharia LC, Jackson EK, Gillespie DG, Dubey RK. Catecholamines abrogate the anti-mitogenic effects of 2-hydroxyestradiol on human aortic vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2001;21(11):1745–50.PubMedGoogle Scholar
  141. 141.
    Dubey RK, Zacharia LC, Gillespie DG, Imthurn B, Jackson EK. Catecholamines block the antimitogenic effect of estradiol on human glomerular mesangial cells. Hypertension. 2003;42(3):349–55. Epub 2003 Aug 11.PubMedGoogle Scholar
  142. 142.
    Lloyd T, Weisz J. Direct inhibition of tyrosine hydroxylase activity by catechol estrogens. J Biol Chem. 1978;253(14):4841–3.PubMedGoogle Scholar
  143. 143.
    Sudhir K, Elser MD, Jennings GL, Komesaroff PA. Estrogen supplementation decreases norepinephrine-induced vasoconstriction and total body norepinephrine spillover in perimenopausal women. Hypertension. 1997;30(6):1538–43.PubMedGoogle Scholar
  144. 144.
    Komesaroff PA, Esler MD, Sudhir K. Estrogen supplementation attenuates glucocorticoid and catecholamine responses to mental stress in perimenopausal women. J Clin Endocrinol Metab. 1999;84(2):606–10.PubMedGoogle Scholar
  145. 145.
    Ceresini G, Freddi M, Morganti S, Rebecchi I, Modena AB, Rinaldi M, Manca C, Amaducci A, Del Rio G, Valenti G. The effects of transdermal estradiol on the response to mental stress in postmenopausal women: a randomized trial. Am J Med. 2000;109(6):463–8.PubMedGoogle Scholar
  146. 146.
    Menozzi R, et al. Sympathoadrenal response of postmenopausal women prior and during prolonged administration of estradiol. Maturitas. 2000;34:275–28.PubMedGoogle Scholar
  147. 147.
    Wang PN, Liu HC, Liu TY, Chu A, Hong CJ, Lin KN, Chi CW. Estrogen-metabolizing gene COMT polymorphism synergistic APOE epsilon4 allele increases the risk of Alzheimer disease. Dement Geriatr Cogn Disord. 2005;19(2–3):120–5. Epub 2004 Dec 9.PubMedGoogle Scholar
  148. 148.
    Rothe C, Koszycki D, Bradwejn J, King N, Deluca V, Tharmalingam S, Macciardi F, Deckert J, Kennedy JL. Association of the Val158Met catechol-O-methyltransferase genetic polymorphism with panic disorder. Neuropsychopharmacology. 2006;31(10):2237–42. Epub 2006 Mar 8.PubMedGoogle Scholar
  149. 149.
    Colilla S, Lerman C, Shields PG, Jepson C, Rukstalis M, Berlin J, DeMichele A, Bunin G, Strom BL, Rebbeck TR. Association of catechol-O-methyltransferase with smoking cessation in two independent studies of women. Pharmacogenet Genomics. 2005;15(6):393–8.PubMedGoogle Scholar
  150. 150.
    Weinshilboum RM, Otterness DM, Aksoy IA, Wood TC, Her C, Raftogianis RB. Sulfation and sulfotransferases 1: Sulfotransferase molecular biology: cDNAs and genes. FASEB J. 1997;11(1):3–14.PubMedGoogle Scholar
  151. 151.
    Adjei AA, Weinshilboum RM. Catecholestrogen sulfation: possible role in carcinogenesis. Biochem Biophys Res Commun. 2002;292(2):402–8.PubMedGoogle Scholar
  152. 152.
    Aksoy IA, Wood TC, Weinshilboum R. Human liver estrogen sulfotransferase: identification by cDNA cloning and expression. Biochem Biophys Res Commun. 1994;200(3):1621–9.PubMedGoogle Scholar
  153. 153.
    Falany JL, Falany CN. Expression of cytosolic sulfotransferases in normal mammary epithelial cells and breast cancer cell lines. Cancer Res. 1996;56(7):1551–5.PubMedGoogle Scholar
  154. 154.
    Hernández JS, Watson RW, Wood TC, Weinshilboum RM. Sulfation of estrone and 17 beta-estradiol in human liver. Catalysis by thermostable phenol sulfotransferase and by dehydroepiandrosterone sulfotransferase. Drug Metab Dispos. 1992;20(3):413–22.PubMedGoogle Scholar
  155. 155.
    Falany JL, Lawing L, Falany CN. Identification and characterization of cytosolic sulfotransferase activities in MCF-7 human breast carcinoma cells. J Steroid Biochem Mol Biol. 1993;46(4):481–7.PubMedGoogle Scholar
  156. 156.
    Sharp S, Anderson JM, Coughtrie MW. Immunohistochemical localisation of hydroxysteroid sulphotransferase in human breast carcinoma tissue: a preliminary study. Eur J Cancer. 1994;30A(11):1654–9.PubMedGoogle Scholar
  157. 157.
    Falany CN, Wheeler J, Oh TS, Falany JL. Steroid sulfation by expressed human cytosolic sulfotransferases. J Steroid Biochem Mol Biol. 1994;48(4):369–75.PubMedGoogle Scholar
  158. 158.
    Spink BC, Katz BH, Hussain MM, Pang S, Connor SP, Aldous KM, Gierthy JF, Spink DC. SULT1A1 catalyzes 2-methoxyestradiol sulfonation in MCF-7 breast cancer cells. Carcinogenesis. 2000;21(11):1947–57.PubMedGoogle Scholar
  159. 159.
    Raftogianis RB, Wood TC, Otterness DM, Van Loon JA, Weinshilboum RM. Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype. Biochem Biophys Res Commun. 1997;239(1):298–304.PubMedGoogle Scholar
  160. 160.
    Raftogianis RB, Wood TC, Weinshilboum RM. Human phenol sulfotransferases SULT1A2 and SULT1A1: genetic polymorphisms, allozyme properties, and human liver genotype–phenotype correlations. Biochem Pharmacol. 1999;58(4):605–16.PubMedGoogle Scholar
  161. 161.
    Carlini EJ, Raftogianis RB, Wood TC, Jin F, Zheng W, Rebbeck TR, Weinshilboum RM. Sulfation pharmacogenetics: SULT1A1 and SULT1A2 allele frequencies in Caucasian, Chinese and African-American subjects. Pharmacogenetics. 2001;11(1):57–68.PubMedGoogle Scholar
  162. 162.
    Seth P, Lunetta KL, Bell DW, Gray H, Nasser SM, Rhei E, Kaelin CM, Iglehart DJ, Marks JR, Garber JE, Haber DA, Polyak K. Phenol sulfotransferases: hormonal regulation, polymorphism, and age of onset of breast cancer. Cancer Res. 2000;60(24):6859–63.PubMedGoogle Scholar
  163. 163.
    Langsenlehner U, Krippl P, Renner W, Yazdani-Biuki B, Eder T, Wolf G, Wascher TC, Paulweber B, Weitzer W, Samonigg H. Genetic variants of the sulfotransferase 1A1 and breast cancer risk. Breast Cancer Res Treat. 2004;87(1):19–22.PubMedGoogle Scholar
  164. 164.
    Zheng W, Xie D, Cerhan JR, Sellers TA, Wen W, Folsom AR. Sulfotransferase 1A1 polymorphism, endogenous estrogen exposure, well-done meat intake, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2001;10(2):89–94.PubMedGoogle Scholar
  165. 165.
    Tang D, Rundle A, Mooney L, Cho S, Schnabel F, Estabrook A, Kelly A, Levine R, Hibshoosh H, Perera F. Sulfotransferase 1A1 (SULT1A1) polymorphism, PAH-DNA adduct levels in breast tissue and breast cancer risk in a case–control study. Breast Cancer Res Treat. 2003;78(2):217–22.PubMedGoogle Scholar
  166. 166.
    Lépine J, Bernard O, Plante M, Têtu B, Pelletier G, Labrie F, Bélanger A, Guillemette C. Specificity and regioselectivity of the conjugation of estradiol, estrone, and their catecholestrogen and methoxyestrogen metabolites by human uridine diphospho-glucuronosyltransferases expressed in endometrium. J Clin Endocrinol Metab. 2004;89(10):5222–32.PubMedGoogle Scholar
  167. 167.
    Ebner T, Remmel RP, Burchell B. Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol Pharmacol. 1993;43(4):649–54.PubMedGoogle Scholar
  168. 168.
    Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, Owens IS. A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J Biol Chem. 1992;267(5):3257–61.PubMedGoogle Scholar
  169. 169.
    Guillemette C, Millikan RC, Newman B, Housman DE. Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and association with breast cancer among African Americans. Cancer Res. 2000;60(4):950–6.PubMedGoogle Scholar
  170. 170.
  171. 171.
    Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, Lindhout D, Tytgat GN, Jansen PL, Oude Elferink RP, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med. 1995;333(18):1171–5.PubMedGoogle Scholar
  172. 172.
    Mackenzie PI, Owens IS, Burchell B, Bock KW, Bairoch A, Bélanger A, Fournel-Gigleux S, Green M, Hum DW, Iyanagi T, Lancet D, Louisot P, Magdalou J, Chowdhury JR, Ritter JK, Schachter H, Tephly TR, Tipton KF, Nebert DW. The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics. 1997;7(4):255–69.PubMedGoogle Scholar
  173. 173.
    Beutler E, Gelbart T, Demina A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci U S A. 1998;95(14):8170–4.PubMedGoogle Scholar
  174. 174.
    Iolascon A, Faienza MF, Centra M, Storelli S, Zelante L, Savoia A. (TA)8 allele in the UGT1A1 gene promoter of a Caucasian with Gilbert’s syndrome. Haematologica. 1999;84(2):106–9.PubMedGoogle Scholar
  175. 175.
    Guillemette C, De Vivo I, Hankinson SE, Haiman CA, Spiegelman D, Housman DE, Hunter DJ. Association of genetic polymorphisms in UGT1A1 with breast cancer and plasma hormone levels. Cancer Epidemiol Biomarkers Prev. 2001;10(6):711–4.PubMedGoogle Scholar
  176. 176.
    Fisher MB, Vandenbranden M, Findlay K, Burchell B, Thummel KE, Hall SD, Wrighton SA. Tissue distribution and interindividual variation in human UDP-glucuronosyltransferase activity: relationship between UGT1A1 promoter genotype and variability in a liver bank. Pharmacogenetics. 2000;10(8):727–39.PubMedGoogle Scholar
  177. 177.
    Adegoke OJ, Shu XO, Gao YT, Cai Q, Breyer J, Smith J, Zheng W. Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) and risk of breast cancer. Breast Cancer Res Treat. 2004;85(3):239–45.PubMedGoogle Scholar
  178. 178.
    Sparks R, Ulrich CM, Bigler J, Tworoger SS, Yasui Y, Rajan KB, Porter P, Stanczyk FZ, Ballard-Barbash R, Yuan X, Lin MG, McVarish L, Aiello EJ, McTiernan A. UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients. Breast Cancer Res. 2004;6(5):R488–98. Epub 2004 Jun 29.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Johannes C. Huber
    • 1
  • Eva-Katrin Tempfer-Bentz
    • 1
  • Johannes Ott
    • 1
  • Clemens B. Tempfer
    • 1
  1. 1.Department of Gynaecologic Endocrinology and Reproductive MedicineUniversity of Vienna School of MedicineViennaAustria

Personalised recommendations