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Cytochrome P4501A1 genetic polymorphisms and breast cancer risk in Nigerian women

  • Epidemiology
  • Published:
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Summary

In this case-control study based on 250 women with breast cancer and 250 age-matched controls, we sought to evaluate the role of four polymorphic variants in the CYP1A1 gene in breast cancer susceptibility in Nigerian women. Heterozygosity for the CYP1A1 M1 genotype (CYP1A1 M1 [T/C]) was associated with a 21% reduced risk of breast cancer (OR=0.79, 95% CI 0.46–1.40) while homozygosity for the genotype (CYP1A1 M1 [C/C]) conferred a non-significant 9% reduced risk of breast cancer. These risk profiles were not significantly altered in subgroup analysis by menopausal status. While heterozygosity for the CYP1A1 M3 genotype (T/C) conferred a non-significant 24% reduced risk of breast cancer (OR=0.76, 95% CI 0.47–1.22), homozygosity for the variant was associated a non-significant 1.95-fold increased risk of breast cancer (OR=1.95, 95% CI 0.24–6.01). Subgroup analysis showed a non-significant 11% reduced risk in premenopausal heterozygous carriers (OR=0.89, 95% CI 0.45–1.44) and a non-significant 6% increased risk of postmenopausal breast cancer for carriers of the CYP1A1 M3 (T/C) genotype. The CYP1A1 M2 (isoleucine to valine) polymorphism in exon 7 and CYP1A1 M4 (threonine to asparagine) variant in codon 461 of the CYP1A1 gene were found to be very rare in our study subjects. This study has shown that while the CYP1A1 M1 polymorphism conferred reduced risk of breast cancer, homozygosity for the CYP1A1 M3 (C/C) was associated with increased risk of breast cancer although these risks did not attain statistical significance.

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References

  1. Kawajiri K, Nakachi K, Imai K, Yoshii A, Shinoda N, Wanatabe J, 1990 Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P4501A1 gene FEBS Lett 263: 131–133

    Article  PubMed  CAS  Google Scholar 

  2. Hayashi S, Wanatabe J, Nakachi K, Kawajiri K, 1991, Genetic linkage of lung-associated MspI polymorphism with amino acid replacement in the heme binding region of the human cytochrome P4501A1 gene J Biochem 110: 407–411

    PubMed  CAS  Google Scholar 

  3. Crofts F, Cosma GN, Currie D, Taioli E, Toniolo P, Garte SJ, 1993 A novel CYP1A1 gene polymorphism in African-Americans Carcinogenesis 14: 1729–1731

    Article  PubMed  CAS  Google Scholar 

  4. Cascorbi I, Brockmoller J, Roots I, 1996 A C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkages, and impact on lung cancer susceptibility Cancer Res 56: 4965–4969

    PubMed  CAS  Google Scholar 

  5. Schneider J, Huh MM, Bradlow LH, Fishman J, 1984 Antiestrogen action of 2-hydrxyestrone on MCF-7 human breast cancer cells J Biol Chem 259: 4840–4845

    PubMed  CAS  Google Scholar 

  6. Fotsis T, Zhang Y, Pepper MS, Aldercreutz H, Montesano R, Nawroth PP, Schwelgerer L, 1994 The endogenous estrogen metabolite 2-methoxyestradiol inhibits angiogenesis and suppresses tumor growth Nature 368: 237–239

    Article  PubMed  CAS  Google Scholar 

  7. Cushman M, He HM, Katzenellenbogan JA, Lin CM, Hamel E, 1995 Synthesis, antitubulin and antimitotic activity, and cytotoxicity of analogs of 2-methoxyestradiol, an endogenous mammalian metabolite of estradiol that inhibits tubulin polymerization by binding to the colchicines binding site J Med Chem 38: 2041–2049

    Article  PubMed  CAS  Google Scholar 

  8. Klauber N, Parangi S, Flymn E, Hamel E, D’Amato RJ, 1997 Inhibition of angiogenesis and breast cancer in mice by the microtubulin inhibitors 2-methoxyestradiol and taxol Cancer Res 57: 81–86

    PubMed  CAS  Google Scholar 

  9. Musey PI, Collins DC, Bradlow HL, et al. 1987 Effect of diet on oxidation of 17beta- estradiol in vivo J Clin Endocrinol Metab 65: 782–795

    Article  Google Scholar 

  10. Gierthy JF, Lincoln DWII, Kampcik SJ, et al. 1988 Enhancement of 2- and 16 alpha-estradiol hydroxylation in MCF-7 human breast cancer cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin Biochem Biophys Res Commun 157: 515–520

    Article  PubMed  CAS  Google Scholar 

  11. Wanatabe H, 1971 Effects of 17 alpha-ethinylestradiol on biliary metabolites of 17 beta[6,7–3H]estradiol in the rat Biochem Biophys Acta 231: 399–405

    PubMed  Google Scholar 

  12. Crofts F, Taioli E, Cosma GN, Currie D, Toniolo P, Garte SJ, 1994 Functional significance of different human CYP1A1 genotypes Carcinogenesis (Lond.), 12: 2961–2963

    Article  Google Scholar 

  13. Taioli E, Trachman J, Chen X, Toniolo P, Garte SJ, 1995 A CYP1A1 restriction fragment length polymorphism is associated with breast cancer in African-American women Cancer Res 55: 3757–3758

    PubMed  CAS  Google Scholar 

  14. Taioli E, Bradlow HL, Garbers SV, Sepkovic DW, Osborne MP, et al. 1999 Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk Cancer Detect Prev 23(3): 232–237

    Article  PubMed  CAS  Google Scholar 

  15. Rebbeck TR, Rosvold EA, Duggan DJ, Zhang J, Buetow KH, 1994 Genetics of CYP1A1: Coamplification of specific alleles by Polymerase Chain Reaction and association with breast cancer Cancer Epidemiol Biomarkers Prev 3: 511–514

    PubMed  CAS  Google Scholar 

  16. Ambrosone CB, Freudenheim JL, Graham S, Marshall JR, Vena JE, Brasue JR, et al. 1995 Cytochrome P4501A1 and Glutathione S-Transferase (M1) genetic polymorphisms and postmenopausal breast cancer risk Cancer Res 55: 3483–3485

    PubMed  CAS  Google Scholar 

  17. Ishibe N, Hankinson SE, Colditz GA, Spiegelman D, Willet WC, et al. 1998 Cigarrete smoking, cytochrome P4501A1 polymorphisms, and breast cancer risk in the Nurses’ Health Study Cancer Res 58: 667–671

    PubMed  CAS  Google Scholar 

  18. Huang CS, Shen CY, Chang KJ, Hsu SM, Chern HD, 1999 Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan Br J Cancer 80(11): 1838–1843

    Article  PubMed  CAS  Google Scholar 

  19. Miyoshi Y, Takahashi Y, Egawa C, Noguchi S, 2002 Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women The Breast J 8(4): 209–215

    Article  CAS  Google Scholar 

  20. QIAamp DNA Mini Kit and QIAamp DNA Blood Mini Kit Handbook, February 2003

  21. QIAamp DNA Midi Kit and QIAamp DNA Blood Midi Kit Handbook, February 2003

  22. Fishman J, Schneider J, Hershcopf RJ, Bradlow HL, 1984 Increased estrogen 16α-hydroxylase activity in women with breast cancer and endometrial cancer J Steroid Biochem Mol Biol 20: 1077–1081

    CAS  Google Scholar 

  23. Yager JD, Liehr JG, 1996 Molecular mechanisms of estrogen carcinogenesis Ann Rev Pharmacol Toxicol 36: 203–232

    Article  CAS  Google Scholar 

  24. Zhu BT, Conney AH, 1998 Functional role of estrogen metabolism in target cells: Review and perspectives Carcinogenesis 19: 1–27

    Article  PubMed  Google Scholar 

  25. Peterson DD, McKinney CE, Ikeya K, Smith HH, et al. 1991 Human CYP1A1 gene: Cosegregation of the enzyme inducibility phenotype and an RFLP Am J Hum Genet 48: 720–725

    PubMed  Google Scholar 

  26. Cosma GN, Crofts F, Currie D, Wirgin I, Toniolo P, Garte SJ, 1993 Racial differences in restriction fragment length polymorphisms and Mrna inducibility of the human CYP1A1 gene Cancer Epidemiol Biomark Prevent 2: 53–57

    CAS  Google Scholar 

  27. Crofts F, Cosma GN, Currie D, Taioli E, Toniolo P, Garte SJ, 1993 A novel CYP1A1 gene polymorphism in African-Americans Carcinogenesis 14(9): 1729–1731

    Article  PubMed  CAS  Google Scholar 

  28. Bailey LR, Roodi N, Verrier CS, Yee CJ, Dupont WD, Parl FF, 1998 Breast cancer and CYP1A1, GSTM1, and GSTT1 polymorphisms: evidence of a lack of association in Caucasians and African-Americans Cancer Res 58: 65–70

    PubMed  CAS  Google Scholar 

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Acknowledgements

This study was supported by a post-doctoral grant awarded to Okobia MN by the U.S. Army Medical and Materiel Command’s Breast Cancer Research Program (Award Number: DAMD17-02-1-0551). We are grateful to the staff of the Departments of Surgery of the Nigerian Study Sites including University of Benin Teaching Hospital, Benin City; Nnamdi Azikiwe University Teaching Hospital, Nnewi; University of Nigeria Teaching Hospital, Enugu; and the University of Port Harcourt Teaching Hospital, Port Harcourt, for all their assistance during the recruitment of study participants. Special thanks to the staff of the Department of Epidemiology, University of Pittsburgh for their invaluable assistance throughout the conduct of this study.

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Authors and Affiliations

  1. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Room A521, Crabtree Hall, 130 Desoto Street, Pittsburgh, PA, 15261, USA

    Michael Okobia, Clareann Bunker, Joseph Zmuda & Lewis Kuller

  2. Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, 15261, USA

    Candace Kammerer & Robert Ferrell

  3. Department of Medicine, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA

    Victor Vogel

  4. Department of Surgery, University of Benin Teaching Hospital, Benin City, Nigeria

    Michael Okobia

  5. Department of Surgery, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria

    Emmanuel Uche

  6. Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria

    Stanley Anyanwu

  7. Department of Surgery, University of Nigeria Teaching Hospital, Enugu, Nigeria

    Emmanuel Ezeome

  8. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Room A521, Crabtree Hall, 130 Desoto Street, Pittsburgh, PA, 15261, USA

    Michael Okobia

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  1. Michael Okobia
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  2. Clareann Bunker
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  8. Emmanuel Ezeome
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  10. Lewis Kuller
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Correspondence to Michael Okobia.

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Okobia, M., Bunker, C., Zmuda, J. et al. Cytochrome P4501A1 genetic polymorphisms and breast cancer risk in Nigerian women. Breast Cancer Res Treat 94, 285–293 (2005). https://doi.org/10.1007/s10549-005-9022-x

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  • DOI: https://doi.org/10.1007/s10549-005-9022-x

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