Archives of Gynecology and Obstetrics

, Volume 274, Issue 6, pp 367–371

Cytochrome P2A13 and P1A1 gene polymorphisms are associated with the occurrence of uterine leiomyoma

  • D. Herr
  • H. Bettendorf
  • D. Denschlag
  • C. Keck
  • D. Pietrowski
Original Article

Abstract

Problem

To investigate the association between the occurrence of uterine leiomyoma and two SNPs of the CYP 2A13 and CYP 1A1 genes.

Method of study

Prospective case control study with 132 women with clinically and surgically diagnosed uterine leiomyoma and 260 controls. Genotyping was performed by polymerase chain reaction (PCR) based amplification of CYP 2A13 and CYP 1A1 genes, and restriction fragment length polymorphism (RFLP) analysis.

Results

Comparing women with uterine leiomyoma and controls, we demonstrate statistical significant differences of allele frequency and genotype distribution for the CYP 1A1 polymorphism (P = 0.025 and P = 0.046, respectively). Furthermore, for the CYP 2A13 polymorphism we found a significant difference concerning allele frequency (P = 0.033). However, for the genotype distribution, only borderline significance was observed (P = 0.064).

Conclusions

The CYP 2A13 and CYP 1A1 SNPs are associated with uterine leiomyoma in a Caucasian population and may contribute to the understanding of the pathogenic mechanisms of uterine leiomyoma.

Keywords

CYP 1A1 CYP 2A13 Leiomyoma Polymorphism 

References

  1. 1.
    Marino JL, Eskenazi B, Warner M, Samuels S, Vercellini P, Gavoni N et al (2004) Uterine leiomyoma and menstrual cycle characteristics in a population-based cohort study. Hum Reprod 19(10):2350–2355PubMedCrossRefGoogle Scholar
  2. 2.
    Sell SM, Tullis C, Stracner D, Song CY, Gewin J (2005) Minimal interval defined on 7q in uterine leiomyoma. Cancer Genet Cytogenet 157(1):67–69PubMedCrossRefGoogle Scholar
  3. 3.
    Townsend DE, Sparkes RS, Baluda MC, McClelland G (1970) Unicellular histogenesis of uterine leiomyomas as determined by electrophoresis by glucose-6-phosphate dehydrogenase. Am J Obstet Gynecol 107(8):1168–1173PubMedGoogle Scholar
  4. 4.
    Wu J, Cheng Y (1995) [Research on the relationship between estrogen receptor, progesterone receptor, cell proliferation associated antigen in uterine leiomyoma and nuclear body density of myoma, serum reproductive hormone concentrations]. Zhonghua Fu Chan Ke Za Zhi 30(10):603–607PubMedGoogle Scholar
  5. 5.
    Jakimiuk AJ, Bogusiewicz M, Tarkowski R, Dziduch P, Adamiak A, Wrobel A et al (2004) Estrogen receptor alpha and beta expression in uterine leiomyomas from premenopausal women. Fertil Steril 82(Suppl 3):1244–1249PubMedCrossRefGoogle Scholar
  6. 6.
    Shastry BS (2002) SNP alleles in human disease and evolution. J Hum Genet 47(11):561–566PubMedCrossRefGoogle Scholar
  7. 7.
    Kelada SN, Eaton DL, Wang SS, Rothman NR, Khoury MJ (2003) The role of genetic polymorphisms in environmental health. Environ Health Perspect 111(8):1055–1064PubMedGoogle Scholar
  8. 8.
    Evans WE, McLeod HL (2003) Pharmacogenomics—drug disposition, drug targets, and side effects. N Engl J Med 348(6):538–549PubMedCrossRefGoogle Scholar
  9. 9.
    Hemminki K, Forsti A, Lorenzo BJ (2005) Single nucleotide polymorphisms (SNPs) are inherited from parents and they measure heritable events. J Carcinog 4(1):2PubMedCrossRefGoogle Scholar
  10. 10.
    Stiborova M, Martinek V, Rydlova H, Koblas T, Hodek P (2005) Expression of cytochrome P450 1A1 and its contribution to oxidation of a potential human carcinogen 1-phenylazo-2-naphthol (Sudan I) in human livers. Cancer Lett 220(2):145–154PubMedCrossRefGoogle Scholar
  11. 11.
    Somner J, McLellan S, Cheung J, Mak YT, Frost ML, Knapp KM et al (2004) Polymorphisms in the P450 c17 (17-hydroxylase/17,20-Lyase) and P450 c19 (aromatase) genes: association with serum sex steroid concentrations and bone mineral density in postmenopausal women. J Clin Endocrinol Metab 89(1):344–351PubMedCrossRefGoogle Scholar
  12. 12.
    Warner M, Hellmold H, Magnusson M, Rylander T, Hedlund E, Gustafsson JA (1998) Extrahepatic cytochrome P450: role in in situ toxicity and cell-specific hormone sensitivity. Arch Toxicol Suppl 20:455–463PubMedGoogle Scholar
  13. 13.
    Sharp L, Cardy AH, Cotton SC, Little J (2004) CYP17 gene polymorphisms: prevalence and associations with hormone levels and related factors. a HuGE review. Am J Epidemiol 160(8):729–740PubMedCrossRefGoogle Scholar
  14. 14.
    Hukkanen J, Mantyla M, Kangas L, Wirta P, Hakkola J, Paakki P et al (1998) Expression of cytochrome P450 genes encoding enzymes active in the metabolism of tamoxifen in human uterine endometrium. Pharmacol Toxicol 82(2):93–97PubMedCrossRefGoogle Scholar
  15. 15.
    Zhang X, Su T, Zhang QY, Gu J, Caggana M, Li H et al (2002) Genetic polymorphisms of the human CYP2A13 gene: identification of single-nucleotide polymorphisms and functional characterization of an Arg257Cys variant. J Pharmacol Exp Ther 302(2):416–423PubMedCrossRefGoogle Scholar
  16. 16.
    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(21):4965–4969PubMedGoogle Scholar
  17. 17.
    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(17):3757–3758PubMedGoogle Scholar
  18. 18.
    Esteller M, Garcia A, Martinez-Palones JM, Xercavins J, Reventos J (1997) Germ line polymorphisms in cytochrome-P450 1A1 (C4887 CYP1A1) and methylenetetrahydrofolate reductase (MTHFR) genes and endometrial cancer susceptibility. Carcinogenesis 18(12):2307–2311PubMedCrossRefGoogle Scholar
  19. 19.
    Watanabe J, Shimada T, Gillam EM, Ikuta T, Suemasu K, Higashi Y et al (2000) Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer. Pharmacogenetics 10(1):25–33PubMedCrossRefGoogle Scholar
  20. 20.
    Goodman MT, McDuffie K, Kolonel LN, Terada K, Donlon TA, Wilkens LR et al (2001) Case–control study of ovarian cancer and polymorphisms in genes involved in catecholestrogen formation and metabolism. Cancer Epidemiol Biomarkers Prev 10(3):209–216PubMedGoogle Scholar
  21. 21.
    Krajinovic M, Ghadirian P, Richer C, Sinnett H, Gandini S, Perret C et al (2001) Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene–environment interactions. Int J Cancer 92(2):220–225PubMedCrossRefGoogle Scholar
  22. 22.
    Chang BL, Zheng SL, Isaacs SD, Turner A, Hawkins GA, Wiley KE et al (2003) Polymorphisms in the CYP1A1 gene are associated with prostate cancer risk. Int J Cancer 106(3):375–378PubMedCrossRefGoogle Scholar
  23. 23.
    Hefler LA, Grimm C, Heinze G, Schneeberger C, Mueller MW, Muendlein A et al (2005) Estrogen-metabolizing gene polymorphisms and age at natural menopause in Caucasian women. Hum Reprod 20(5):1422–1427PubMedCrossRefGoogle Scholar
  24. 24.
    Amant F, Dorfling CM, de Brabanter J, Vandewalle J, Vergote I, Lindeque BG et al (2004) A possible role of the cytochrome P450c17alpha gene (CYP17) polymorphism in the pathobiology of uterine leiomyomas from black South African women: a pilot study. Acta Obstet Gynecol Scand 83(3):234–239PubMedCrossRefGoogle Scholar
  25. 25.
    Hadfield RM, Manek S, Nakago S, Mukherjee S, Weeks DE, Mardon HJ et al (1999) Absence of a relationship between endometriosis and the N314D polymorphism of galactose-1-phosphate uridyl transferase in a UK population. Mol Hum Reprod 5(10):990–993PubMedCrossRefGoogle Scholar
  26. 26.
    Hadfield RM, Manek S, Weeks DE, Mardon HJ, Barlow DH, Kennedy SH (2001) Linkage and association studies of the relationship between endometriosis and genes encoding the detoxification enzymes GSTM1, GSTT1 and CYP1A1. Mol Hum Reprod 7(11):1073–1078PubMedCrossRefGoogle Scholar
  27. 27.
    Ishii K, Takakuwa K, Kashima K, Tamura M, Tanaka K (2003) Associations between patients with endometriosis and HLA class II; the analysis of HLA-DQB1 and HLA-DPB1 genotypes. Hum Reprod 18(5):985–989PubMedCrossRefGoogle Scholar
  28. 28.
    Nakago S, Hadfield RM, Zondervan KT, Mardon H, Manek S, Weeks DE et al (2001) Association between endometriosis and N-acetyl transferase 2 polymorphisms in a UK population. Mol Hum Reprod 7(11):1079–1083PubMedCrossRefGoogle Scholar
  29. 29.
    Ishii K, Takakuwa K, Mitsui T, Tanaka K (2002) Studies on the human leukocyte antigen-DR in patients with endometriosis: genotyping of HLA-DRB1 alleles. Hum Reprod 17(3):560–563PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • D. Herr
    • 1
    • 2
    • 3
  • H. Bettendorf
    • 2
  • D. Denschlag
    • 2
  • C. Keck
    • 2
  • D. Pietrowski
    • 2
  1. 1.Department of Obstetrics and GynecologyUlm University Medical CenterUlmGermany
  2. 2.Department of Obstetrics and GynecologyFreiburg University Medical CenterFreiburgGermany
  3. 3.Universitäts-Frauenklinik UlmUlmGermany

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