Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Lack of Influence of the ACE1 Gene I/D Polymorphism on the Formation and Growth of Benign Uterine Leiomyoma in Turkish Patients

  • Gultekin, Guldal Inal (Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University) ;
  • Yilmaz, Seda Gulec (Department of Molecular Medicine, Institute of Health Sciences, Faculty of Medicine, Yeditepe University) ;
  • Kahraman, Ozlem Timirci (Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University) ;
  • Atasoy, Hande (Department of Molecular Medicine, Institute of Health Sciences, Faculty of Medicine, Yeditepe University) ;
  • Dalan, A. Burak (Yeditepe University Hospital, Faculty of Medicine, Yeditepe University) ;
  • Attar, Rukset (Department of Gynecology, Faculty of Medicine, Yeditepe University) ;
  • Buyukoren, Ahmet (Department of Gynecology, Faculty of Medicine, Istanbul University) ;
  • Ucunoglu, Nazli (Department of Molecular Medicine, Institute of Health Sciences, Faculty of Medicine, Yeditepe University) ;
  • Isbir, Turgay (Department of Medical Biology, Faculty of Medicine, Yeditepe University)
  • Published : 2015.03.04
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Abstract

Uterine leiomyomas (ULM), are benign tumors of the smooth muscle cells of the myometrium. They represent a common health problem and are estimated to be present in 30-70% of clinically reproductive women. Abnormal angiogenesis and vascular-related growth factors have been suggested to be associated with ULM growth. The angiotensin-I converting enzyme (ACE) is related with several tumors. The aim of this study was to identify possible correlation between ULM and the ACE I/D polymorphism, to evaluate whether the ACE I/D polymorphism could be a marker for early diagnosis and prognosis. ACE I/D was amplified with specific primer sets recognizing genomic DNA from ULM (n=72) and control (n=83) volunteers and amplicons were separated on agarose gels. The observed genotype frequencies were in agreement with Hardy-Weinberg equilibrium ($x^2=2.162$, p=0.339). There was no association between allele frequencies and study groups ($x^2=0.623$; p=0.430 for ACE I allele, $x^2=0.995$; p=0.339 for ACE D allele). In addition, there were no significant differences between ACE I/D polymorphism genotype frequencies and ULM range in size and number ($X^2=1.760;$ p=0.415 for fibroid size, $X^2=0.342;$ p=0.843 for fibroid number). We conclude that the ACE gene I/D polymorphism is not related with the size or number of ULM fibroids in Turkish women. Thus it cannot be regarded as an early diagnostic parameter nor as a risk estimate for ULM predisposition.

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References

  1. Alvarez R, Terrados N, Ortolano R, et al (2000). Genetic variation in the renin-angiotensin system and athletic performance. Eur J Appl Physiol, 82, 117-120. https://doi.org/10.1007/s004210050660
  2. Ates O, Demirturk F, Toprak M, et al (2013). Polymorphism of catechol-o-methyltransferase and uterine leiomyoma. Mol Cell Biochem, 375, 179-83.
  3. Baird DD, Dunson DB, Hill MC, et al (2000). High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol, 188, 100-7.
  4. Bayram B, Kilicci C, Onlu H, et al (2011). Association of angiotensin converting enzyme (ACE) gene I/D polymorphism and polycystic ovary syndrome (PCOS). Gene, 489, 86-8. https://doi.org/10.1016/j.gene.2011.08.012
  5. Cardozo ER, Clark AD, Banks NK, et al (2012). The estimated annual cost of uterine leiomyomata in the United States. Am J Obstet Gynecol, 206, 1-9. https://doi.org/10.1016/j.ajog.2011.10.025
  6. Catherino WH, Eltoukhi HM, Al-Hendy A (2013). Racial and ethnic differences in the pathogenesis and clinical manifestations of uterine leiomyoma. Semin Reprod Med, 31, 370-9. https://doi.org/10.1055/s-0033-1348896
  7. Cha PC, Takahashi A, Hosono N, et al (2011). A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids. Nat Genet, 43, 447-50. https://doi.org/10.1038/ng.805
  8. Cheng Z, Ma R, Tan W, et al (2014). Lack of association between ACE insertion/deletion polymorphism and lung cancer: A meta-analysis. J Renin Angiotensin Aldosterone Syst, [Epub ahead of print].
  9. Di Lieto A, De Falco M, Pollio F, et al (2005). Clinical response, vascular change, and angiogenesis in gonadotropin-releasing hormone analogue- treated women with uterine myomas. J Soc Gynecol Investig, 12, 123-8. https://doi.org/10.1016/j.jsgi.2004.10.008
  10. Dinh DT, Frauman AG, Johnston CI, et al (2001). Angiotensin receptors: distribution, signaling and function. Clin Sci (Lond), 100, 481-92. https://doi.org/10.1042/CS20000263
  11. Edwards TL, Michels KA, Hartmann KE, et al (2013). BET1L and TNRC6B associate with uterine fibroid risk among European Americans. Hum Genet, 132, 943-53. https://doi.org/10.1007/s00439-013-1306-3
  12. Ekin M. Cengiz H, Ozturk E, et al (2014). Genitourinary symptoms and their effects on quality of life in women with uterine myomas. Int Urogynecol J, 25, 807-10. https://doi.org/10.1007/s00192-013-2295-4
  13. Ergen HA, Hatemi H, Agachan B, et al (2004). Angiotensin-I converting enzyme gene polymorphism in Turkish type 2 diabetic patients. Exp Mol Med, 36, 345-50. https://doi.org/10.1038/emm.2004.45
  14. Fernandez LA, Twickler J, Mead A (1985). Neovascularization produced by angiotensin II. J Lab Clin Med, 105, 141-5.
  15. Fishchuk LE, Gorovenko NG (2013). Genetic polymorphisms of the renin-angiotensin system in breast cancer patients. Exp Oncol, 35, 101-4.
  16. Flake GP, Andersen J, Dixon D (2003). Etiology and pathogenesis of uterine leiomyomas: a review. Environ Health Perspect, 111, 1037-54.
  17. Freitas-Silva M, Pereira D, Coelho C, et al (2004). Angiotensin I-converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women. Cancer Genet Cytogenet, 155, 42-6. https://doi.org/10.1016/j.cancergencyto.2004.03.020
  18. Gülec-Yilmaz S, Yilmaz H, Dalan AB, et al (2014). The relationship between ACE polymorphism and panic disorder. In Vivo, 28, 885-9.
  19. Hakverdi S, Demirhan O, Tunc E, et al (2013). Chromosome imbalances and alterations in the p53 gene in uterine myomas from the same family members: familial leiomyomatosis in Turkey. Asian Pac J Cancer Prev, 14, 651-8. https://doi.org/10.7314/APJCP.2013.14.2.651
  20. Henskens LH, Spiering W, Stoffers HE, et al (2003). Effects of ACE I/D and AT1R-A1166C polymorphisms on blood pressure in a healthy normotensive primary care population: first results of the hippocates study. J Hypertens, 21, 81-6. https://doi.org/10.1097/00004872-200301000-00017
  21. Herr D, Bekes I, Wulff C (2013). Local renin-angiotensin system in the reproductive system. Front Endocrinol, 4, 1-7.
  22. Hsieh YY, Lee CC, Chang CC, et al (2007). Angiotensin I-converting enzyme insertion-related genotypes and allele are associated with higher susceptibility of endometriosis and leiomyoma. Mol Reprod Dev, 74, 808-14. https://doi.org/10.1002/mrd.20474
  23. Isbir SC, Tekeli A, Ergen A, et al (2007). Genetic polymorphisms contribute to acute kidney injury after coronary artery bypass grafting. Heart Surg Forum, 10, 439-44.
  24. Jia H, Wang B, Yu L, et al (2013). Association of angiotensinconverting enzyme gene insertion/deletion polymorphism with polycystic ovary syndrome: a meta-analysis. J Renin Angiotensin Aldosterone Syst, 14, 255-62. https://doi.org/10.1177/1470320312452768
  25. Li XL, Zheng ZJ, Qu HO (2014). Lack of association of angiotensin-converting enzyme insertion/deletion polymorphism with breast cancer: An update meta-analysis based on 10405 subjects. J Renin Angiotensin Aldosterone Syst, [Epub ahead of print].
  26. Li ZH Pan XM, Han BW, et al (2012). No association between ACE polymorphism and risk of nasopharyngeal carcinoma. J Renin Angiotensin Aldosterone Syst, 13, 210-5. https://doi.org/10.1177/1470320311426168
  27. Liu SY, Sima X, Wang CH, et al (2011). The association between ACE polymorphism and risk of colorectal cancer in a Chinese population. Clin Biochem, 44, 1223-6. https://doi.org/10.1016/j.clinbiochem.2011.07.016
  28. Matsumoto T, Sagawa N, Mukoyama M, et al (1996). Type 2 angiotensin II receptor is expressed in human myometrium and uterine leiomyoma and is down-regulated during pregnancy. J Clin Endocrinol Metab, 81, 4366-72.
  29. Mc Menamin UC, Murray LJ, Cantwell MM, et al (2012). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cancer progression and survival: a systematic review. Cancer Causes Control, 23, 221-30. https://doi.org/10.1007/s10552-011-9881-x
  30. Rigat B, Hubert C, Alhenc-Gelas F, et al (1990). An insertion/ deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest, 86, 1343-6. https://doi.org/10.1172/JCI114844
  31. Rigat B, Hubert C, Corvol P, et al (1992). PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase. Nucleic Acids Res, 20,1433.
  32. Risau W (1997). Mechanisms of angiogenesis. Nature, 386, 671-4. https://doi.org/10.1038/386671a0
  33. Rocken C, Neumann K, Carl-McGrath S, et al (2007). The gene polymorphism of the angiotensin I-converting enzyme correlates with tumor size and patient survival in colorectal cancer patients. Neoplasia, 9, 716-22. https://doi.org/10.1593/neo.07418
  34. Shen Y, Ren ML, Xu J, et al (2014). A multicenter case-control study on screening of single nucleotide polymorphisms in estrogen-metabolizing enzymes and susceptibility to uterine leiomyoma in han chinese. Gynecol Obstet Invest, 77, 224-30. https://doi.org/10.1159/000360083
  35. Tal R, Segars JH (2014). The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy. Hum Reprod Update, 20, 194-216. https://doi.org/10.1093/humupd/dmt042
  36. The National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/gene/1636. Accessed January 2015.
  37. Timmermans PB, Wong PC, Chiu AT, et al (1993). Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev, 45, 205-51.
  38. Vairaktaris E, Serefoglou Z, Avgoustidis D, et al (2009). Gene polymorphisms related to angiogenesis, inflammation and thrombosis that influence risk for oral cancer. Oral Oncol, 45, 247-53. https://doi.org/10.1016/j.oraloncology.2008.05.003
  39. van der Knaap R, Siemes C, Coebergh JW, et al (2008). Reninangiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletionpolymorphism, and cancer: the Rotterdam Study. Cancer, 112, 748-57. https://doi.org/10.1002/cncr.23215
  40. Verit FF, Yucel O (2013). Endometriosis, leiomyoma and adenomyosis: the risk of gynecologic malignancy. Asian Pac J Cancer Prev, 14, 5589-97. https://doi.org/10.7314/APJCP.2013.14.10.5589
  41. Wei MT, Chen N, He YZ, et al (2014). Angiotensin-converting enzyme insertion/deletion polymorphism and gastric cancer: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol, [Epub ahead of print].
  42. Yapijakis C, Koronellos N, Spyridonidou S, et al (2013). Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with decreased risk for basal cell carcinoma. Arch Dermatol Res, 305, 333-9. https://doi.org/10.1007/s00403-012-1312-7
  43. Yuan F, Zhang LS, Li HY, et al (2013). Influence of angiotensin I-converting enzyme gene polymorphism on hepatocellular carcinoma risk in China. DNA Cell Biol, 32, 268-73. https://doi.org/10.1089/dna.2012.1910
  44. Zhang K, Cheng D, Yi L, et al (2014). Association between angiotensin I-converting enzyme gene polymorphism and susceptibility to cancer: a meta analysis. Int J Clin Exp Pathol, 7, 6291-300.