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The Association of the CYP19 and CYP17 Polymorphic Markers with Sporadic Breast Cancer

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Abstract

Polymorphic alleles of CYP17 and CYP19, which are involved in estrogen biosynthesis, were tested for association with breast cancer (BC). Microsatellite (TTTA)n and 3-bp deletion of CYP19 and single-nucleotide polymorphism T27C of CYP17 were analyzed in 123 BC patients and 119 healthy women. Of the six (TTTA)n alleles observed, allele (TTTA)8 proved to be associated with BC (11.8% vs. 6.3%, P = 0.04). Genotype A2/A2 of CYP17 was also associated with BC (32.5% vs. 20.2%, P = 0.04). Risk of BC was especially high in the presence of both factors (7.3% vs. 0%, P < 0.01). Allele (TTTA)8 and genotype A2/A2 were assumed to be risk factors of BC.

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REFERENCES

  1. Trapeznikov N.N., Aksel' E.M. 1998. Novoe v terapii raka molochnoi zhelezy. Statistika raka molochnoi zhelezy (New Achievements in Therapy of Breast Cancer. Statistics of Breast Cancer). Perevodchikova N.I., Ed. Moscow: RON-PULENK RORER, 6–10.

    Google Scholar 

  2. Claus E.B., Risch N., Thompson W.D. 1991. Genetic analysis of breast cancer in the cancer and steroid hormone study. Am. J. Hum. Genet. 48, 232–242.

    Google Scholar 

  3. Ford D., Easton D.F. 1995. The genetics of breast and ovarian cancer. Br. J. Cancer. 72, 805–812.

    Google Scholar 

  4. Dunning A.M., Healey C.S., Pharoah P.D.P., Teare M.D., Ponder B.A.J., Easton D.F. 1999. A systematic review of genetic polymorphisms and breast cancer risk. Cancer Epidemiol. Biomarkers Prev. 8, 843–854.

    Google Scholar 

  5. Pike M.C., Spicer D.V., Dahmoush L., Press M.F. 1993. Estrogens, progestogens, normal breast cell proliferation and breast cancer risk. Epidemiol. Rev. 15, 17–35.

    Google Scholar 

  6. Henderson B.E., Bernstein L. 1996. Endogenous and exogenous hormone factors. In: Diseases and the Breast. Harris J.R. Ed., Philidelphia, PA: Lippincott-Raven, 185–200.

    Google Scholar 

  7. Toniolo P.G., Levitz M., Zeleniuch-Jacquotte A., Banerjee S., Koenig K.L., Shore R.E., Strax P., Pastenack B.A. 1995. A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J. Natl. Cancer Inst. 87, 190–197.

    Google Scholar 

  8. O'Neill J.S., Elton R.A., Miller W.R. 1988. Aromatase activity in adipose tissue from breast quadrants: a link with tumour site. Br. Med. J. 296, 741–743.

    Google Scholar 

  9. Bulun S.E., Price T.M., Mahendroo M.S., Aitken J., Simpson E.R. 1993. A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J. Clin. Endocrinol. Metab. 77, 1622–1628.

    Google Scholar 

  10. Bulun S.E., Simpson E.R. 1999. Regulation of the CYP19 (P450arom) gene expression in breast adipose tissue and breast cancer. Trends Endocrinol. Metab. 10, 9–13.

    Google Scholar 

  11. Pike M.C., Spicer D.V., Dahmoush L., Press M.F. 1993. Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol. Rev. 15, 17–35.

    Google Scholar 

  12. Brentano S.T., Picado-Leonard J., Mellon S.H., Moore C.C., Miller W.L. 1990. Tissue-specific, cyclic adenosine 3',5'-monophosphate-induced, and phorbol ester-repressed transcription from the human P450c17 promoter in mouse cells. Mol. Endocrinol. 4, 1972–1979.

    Google Scholar 

  13. Carey A.H., Waterworth D., Patel K., White D., Little J., Novelli P., Franks S., Williamson R. 1994. Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17. Hum. Mol. Genet. 3, 1873–1876.

    Google Scholar 

  14. Feigelson H.S., Shames L.S., Pike M.C., Coetzee G.A., Stanczyk F.Z., Henderson B.E. 1998. Cytochrome P450c17 gene (CYP17) polymorphism is associated with serum estrogen and progesterone concentrations. Cancer Res. 58, 585–587.

    Google Scholar 

  15. Haiman C.A., Hankinson S.E., Spiegelman D., Colditz G.A., Willett W.C., Speizer F.E., Kelsey K.T., Hunter D.J. 1999. The relationship between a polymorphism in CYP17 with plasma hormone levels and breast cancer. Cancer Res. 59, 1015–1020.

    Google Scholar 

  16. Feigelson H.S., McKean-Cowdin R., Coetzee G.A., Stram D.O., Kolonel L.N., Henderson B.E. 2001. Building a multigenic model of breast cancer susceptibility: CYP17 and HSD17B1 are two important candidates. Cancer Res. 61, 785–789.

    Google Scholar 

  17. Kristensen V.N., Haraldsen E.K., Anderson K.B., Lonning P.E., Erikstein B., Karesen R., Gabrielsen O.S., Borresen-Dale A.-L. 1999. CYP17 and breast cancer risk: the polymorphism in the 5'-flanking area of the gene does not influence binding to Sp-1. Cancer Res. 59, 2825–2828.

    Google Scholar 

  18. Feigelson H.S., Coetzee G.A., Kolonel L.N., Ross R.K., Henderson B.E. 1997. A polymorphism in the CYP17 gene increases the risk of breast cancer. Cancer Res. 57, 1063–1065.

    Google Scholar 

  19. Dunning A.M., Healey C.S., Pharoah P.D., Foster N.A., Lipscombe J.M., Redman K.L., Easton D.F., Day N.E., Ponder B.A. 1998. No association between a polymor-phism in the steroid metabolism gene CYP17 and risk of breast cancer. Br. J. Cancer. 77, 2045–2047.

    Google Scholar 

  20. Huang C.-S., Chern H.-D., Chang K.-J., Cheng C.-W., Hsu S.-M., Shen C.-Y. 1999. Breast cancer risk associated with genotype polymorphisms of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. Cancer Res. 59, 4870–4875.

    Google Scholar 

  21. Thompson E.A., Jr., Siiteri P.K. 1974. Utilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placental microsomes during aromatization of androstenedione. J. Biol. Chem. 249, 5364–5372.

    Google Scholar 

  22. Grodin J.M., Siiteri P.K., MacDonald P.C. 1973. Source of estrogen production in postmenopausal women. J. Clin. Endocrinol. Metab. 38, 207–214.

    Google Scholar 

  23. Bulun S.E., Simpson E.R. 1994. Competitive reverse transcription-polymerase chain reaction analysis indicates that levels of aromatase cytochrome P450 transcripts in adipose tissue of buttocks, thighs, and abdomen of women increase with advancing age. J. Clin. Endocrinol. Metab. 78, 428–432.

    Google Scholar 

  24. Siegelmann-Danieli N., Buetow K.H. 1999. Constitutional genetic variation at the human aromatase gene (CYP19) and breast cancer risk. Br. J. Cancer. 79, 456–463.

    Google Scholar 

  25. Baxter S.W., Choong D.Y.H., Eccles D.M., Campbell I.G. 2001. Polymorphic variation in CYP19 and the risk of breast cancer. Carcinogenesis. 22, 347–349.

    Google Scholar 

  26. Haiman C.A., Hankinson S.E., Speigelman D., De Vivo I., Colditz G.A., Willett W.C., Speizer F.E., Hunter D.J. 2000. A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk. Int. J. Cancer. 87, 204–210.

    Google Scholar 

  27. Kristensen V.N., Andersen T.I., Lindblom A., Erik-stein B., Magnus P., Borresen-Dale A.L. 1998. A rare CYP19 (aromatase) variant may increase the risk of breast cancer. Pharmacogenetics. 8, 43–48.

    Google Scholar 

  28. Miyoshi Y., Iwao K., Ikeda N., Egawa C., Noguchi S. 2000. Breast cancer risk associated with polymorphism in CYP19 in Japanese women. Int. J. Cancer. 89, 325–328.

    Google Scholar 

  29. Healey C.S., Dunning A.M., Durocher F., Teare D., Pharoah P.D., Luben R.N., Easton D.F., Ponder B.A. 2000. Polymorphisms in the human aromatase cyto-chrome P450 gene (CYP19) and breast cancer risk. Carcinogenesis. 21, 189–193.

    Google Scholar 

  30. Suspitsin E.N., Grigoriev M.Y., Togo A.V., Kuligina E.S., Belogubova E.V., Pozharisski K.M., Chagunova O.L., Sokolov E.P., Theillet C., Berstein L.M., Hanson K.P., Imyanitov E.N. 2002. Distinct prevalence of the CYP19 Δ3(TTTA)7 allele in premenopausal vs. postmenopausal breast cancer patients, but not in control individuals. Eur. J. Cancer. 38, 1911–1916.

    Google Scholar 

  31. Sambrook J., Fritsh E.F., Maniatis T. 1989. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, N.Y.: Cold Spring Harbor.

    Google Scholar 

  32. Haiman C.A, Brown M., Hankinson S.E., Spiegelman D., Colditz G.A., Willett W.C., Kantoff P.C., Hunter D.J. 2002. The androgen receptor CAG repeat polymorphism and risk of breast cancer in the Nurses’ Health Study. Cancer Res. 62, 1045–1049.

    Google Scholar 

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Authors and Affiliations

  1. Research Center for Medical Genetics, Russian Academy of Medical Sciences, Moscow, 115478, Russia

    V. V. Artamonov, M. V. Nemtsova & D. V. Zaletaev

  2. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia

    L. N. Lyubchenko & M. A. Shabanov

  3. Institute of Molecular Medicine, Sechenov Medical Academy, Ministry of Health of the Russian Federation, Moscow, 119992, Russia

    O. V. Babenko & D. V. Zaletaev

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  1. V. V. Artamonov
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  2. L. N. Lyubchenko
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  3. M. A. Shabanov
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  5. M. V. Nemtsova
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  6. D. V. Zaletaev
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Artamonov, V.V., Lyubchenko, L.N., Shabanov, M.A. et al. The Association of the CYP19 and CYP17 Polymorphic Markers with Sporadic Breast Cancer. Molecular Biology 37, 830–835 (2003). https://doi.org/10.1023/B:MBIL.0000008350.81352.7e

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  • DOI: https://doi.org/10.1023/B:MBIL.0000008350.81352.7e

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