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Val153Met Polymorphism of Catechol-O-Methyltransferase and Prevalence of Uterine Leiomyomata

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Abstract

The catechol-O-methyltransferase (COMT) gene encodes enzymes that inactivate catechol estrogens and may have a protective role in estrogen-induced tumorigenesis, such as uterine leiomyoma (fibroids). Val158Met is a common single-nucleotide polymorphism of the COMT gene (Ex4-12 G > A; rs4680) that results in a lower activity enzyme, increasing susceptibility to tumorigenesis. The purpose of this study was to evaluate the relation between the COMTVal158Met polymorphism and uterine fibroids. Participants were 972 premenopausal African American (n = 576) and white (n = 396) women from a cross-sectional sample of women in the National Institute of Environmental Health Science’s Uterine Fibroid Study. Blood was collected from participants for DNA, and telephone interviews and questionnaires were completed to gather demographic and reproductive history. Prevalence ratios and 95% confidence intervals were estimated using race-specific log-risk regression models. Effect measure modification by age, body mass index, oral contraceptive use, full-term births, smoking, and alcohol use were also evaluated. Distributions of genotypes and fibroid prevalence varied by race. No associations between fibroids and Val158Met were observed among African American or white participants. This study suggests that variation in this polymorphism alone does not affect fibroid prevalence. Additional research is needed to examine other variations and haplotypes within the COMT gene.

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References

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

    CAS  PubMed  Google Scholar 

  2. Yue TL, Wang X., Louden CS, et al. 2-Methoxyestradiol, an endogenous estrogen metabolite, induces apoptosis in endothelial cells and inhibits angiogenesis: possible role for stress-activated protein kinase signaling pathway and Fas expression. Mol Pharmacol. 1997;51:951–962.

    Article  CAS  PubMed  Google Scholar 

  3. LaVallee TM, Zhan XH, Herbstritt CJ, Kough EC, Green SJ, Pribluda VS 2-Methoxyestradiol inhibits proliferation and induces apoptosis independently of estrogen receptors alpha and beta. Cancer Res. 2002;62:3691–3697.

    CAS  PubMed  Google Scholar 

  4. Pribluda VS, Gubish ER Jr, Lavallee TM, Treston A., Swartz GM, Green SJ 2-Methoxyestradiol: an endogenous antiangiogenic and antiproliferative drug candidate. Cancer Metastasis Rev. 2000;19:173–179.

    Article  CAS  PubMed  Google Scholar 

  5. Axelrod J., Tomchick R. Enzymatic O-methylation of epinephrine and catechols. J Biol Chem. 1958;233:702–705.

    CAS  PubMed  Google Scholar 

  6. Hong CC, Thompson HJ, Jiang C., et al. Val158Met polymorphism in catechol-O-methyltransferase gene associated with risk factors for breast cancer. Cancer Epidemiol Biomarkers Prev. 2003;12:838–847.

    CAS  PubMed  Google Scholar 

  7. Huang CS, Chern HD, Chang KJ, Cheng CW, Hsu SM, Shen CY Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. Cancer Res. 1999;59:4870–4875.

    CAS  PubMed  Google Scholar 

  8. Thompson PA, Shields PG, Freudenheim JL, et al. Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk. Cancer Res. 1998;58: 2107–2110.

    CAS  PubMed  Google Scholar 

  9. Al-Hendy A., Salama SA Catechol-O-methyltransferase polymorphism is associated with increased uterine leiomyoma risk in different ethnic groups. J Soc Gynecol Investig. 2006;13:136–144.

    Article  CAS  PubMed  Google Scholar 

  10. Baird DD, Dunson DB, Hill MC, Cousins D., Schectman JM High cumulative incidence of uterine lieomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003;188:100–107.

    Article  PubMed  Google Scholar 

  11. Baird DD, Dunson DB Why is parity protective for uterine fibroids? Epidemiology. 2003;14:247–250.

    PubMed  Google Scholar 

  12. Ross P., Hall L., Smirnov I., Haff L. High-level multiplex genotyping by MALDI-TOF mass spectrometry. Nat Biotechnol. 1998;16:1347–1351.

    Article  CAS  PubMed  Google Scholar 

  13. Thompson ML, Myers JE, Kriebel D. Prevalence odds ratio or prevalence ratio in the analysis of cross sectional data: what is to be done? Occup Environ Med. 1998;55:272–277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rothman K., Greenland S. Modern Epidemiology. 2nd ed. Philadelphia, Pa: Lippincott-Raven; 1998.

    Google Scholar 

  15. Kjerulff KH, Lagenberg P., Seidman JD, Stolley PD, Guzinski GM Uterine leiomyomas: racial differences in severity, symptoms and age at diagnosis. J Reprod Med. 1996;41:483–490.

    CAS  PubMed  Google Scholar 

  16. Marshall LM, Spiegelman D., Barbieri RL, et al. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet Gynecol. 1997;90:967–973.

    Article  CAS  PubMed  Google Scholar 

  17. Faerstein E., Szklo M., Rosenshein N. Risk factors for uterine leiomyoma: a practice-based case-control study. I. African-American heritage, reproductive history, body size, and smoking. Am J Epidemiol. 2001;153:1–10.

    Article  CAS  PubMed  Google Scholar 

  18. Chen C-R., Buck GM, Courey NG, Perez KM, Wactawski-Wende J. Risk factors for uterine fibroids among women undergoing tubal sterilization. Am J Epidemiol. 2001;153: 20–26.

    Article  CAS  PubMed  Google Scholar 

  19. Wegienka G., Baird DD, Hertz-Picciotto I., et al. Self-reported heavy bleeding associated with uterine leiomyomata. Obstet Gynecol. 2003;101:431–437.

    PubMed  Google Scholar 

  20. Herr D., Bettendorf H., Denschlag D., Keck C., Pietrowski D. Cytochrome P2A13 and P1A1 gene polymorphisms are associated with the occurrence of uterine leiomyoma. Arch Gynecol Obstet. 2006;274:367–371.

    Article  CAS  PubMed  Google Scholar 

  21. Al-Hendy A., Salama SA Ethnic distribution of estrogen receptor-alpha polymorphism is associated with a higher prevalence of uterine leiomyomas in black Americans. Fertil Steril. 2006;86:686–693.

    Article  CAS  PubMed  Google Scholar 

  22. Massart F., Becherini L., Marini F., et al. Analysis of estrogen receptor (ERalpha and ERbeta) and progesterone receptor (PR) polymorphisms in uterine leiomyomas. Med Sci Monit. 2003;9:BR25–BR30.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, USA

    Kyna M. Gooden PhD, Jane C. Schroeder DVM, PhD, Kari E. North PhD, Marilie D. Gammon PhD & Katherine E. Hartmann MD, PhD

  2. Center for Environmental Health and Susceptibility, University of North Carolina, Chapel Hill, USA

    Marilie D. Gammon PhD

  3. Center for Women’s Health Research, University of North Carolina, Chapel Hill, USA

    Katherine E. Hartmann MD, PhD

  4. Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA

    Jack Taylor MD, PhD & Donna D. Baird PhD

Authors
  1. Kyna M. Gooden PhD
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  2. Jane C. Schroeder DVM, PhD
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  3. Kari E. North PhD
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  4. Marilie D. Gammon PhD
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  5. Katherine E. Hartmann MD, PhD
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  6. Jack Taylor MD, PhD
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  7. Donna D. Baird PhD
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Corresponding author

Correspondence to Kyna M. Gooden PhD.

Additional information

The authors thank Honglei Chen and Stephanie London for comments on an earlier version of this article. The Uterine Fibroid Study was managed by Glenn Heartwell, and Deborah Cousins managed the data.

The authors have no personal conflicts of interest to disclose. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences.

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Gooden, K.M., Schroeder, J.C., North, K.E. et al. Val153Met Polymorphism of Catechol-O-Methyltransferase and Prevalence of Uterine Leiomyomata. Reprod. Sci. 14, 117–120 (2007). https://doi.org/10.1177/1933719106298687

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  • DOI: https://doi.org/10.1177/1933719106298687

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