The Polymorphism of Hypoxia-inducible Factor-1a Gene in Endometrial Cancer

  • Kafshdooz, Leila (Women's Reproductive Health Research Center, Department of Medical Genetics, Tabriz University of Medical Sciences) ;
  • Tabrizi, Ali Dastranj (Women's Reproductive Health Research Center, Department of Medical Genetics, Tabriz University of Medical Sciences) ;
  • Mohaddes, Seyyed Mojtaba (Faculty of Medicine, Tabriz University of Medical Sciences) ;
  • Kafshdooz, Tayebeh (Women's Reproductive Health Research Center, Department of Medical Genetics, Tabriz University of Medical Sciences) ;
  • Akbarzadeh, Abolfazl (Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University Of Medical Sciences) ;
  • Ghojazadeh, Morteza (Women's Reproductive Health Research Center, Department of Medical Genetics, Tabriz University of Medical Sciences) ;
  • Gharesouran, Jalal (Faculty of Medicine, Tabriz University of Medical Sciences)
  • Published : 2015.01.06


Background: Endometral carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in women after breast, colorectal and lung cancers Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates cellular response to hypoxia HIF-1 plays important roles in the development and progression of cancer through activation of various genes that are involved in crucial aspects of cancer biology, including angiogenesis, energy metabolism, vasomotor function, erythropoiesis, and cell survival. In this study, we aimed to investigate the association between HIF-1 1772 C/T polymorphisms and endometrial cancer. Materials and Methods: 75 patients with endometrial carcinoma and 75 patients whose underwent hysterectomy for non tumoral indication selected for evaluation of HIF-1 1772 C/T polymorphisms by PCR-RFLP and sequencing. Results: For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with endometrial cancer risk. Conclusions: Our results suggest that the C1772T polymorphism of the HIF-1a may be associated with endometrial cancers.


Endometrial carcinoma;HIF-1a polymorphism


  1. Acmaz G, Aksoy H, Albayrak E, et al (2014). Evaluation of endometrial precancerous lesions in postmenopausal obese women-a high risk group? Asian Pac J Cancer Prev, 15, 195-8.
  2. Balik G, Kagitci M, Ustuner I, et al (2013). Which endometrial pathologies need intraoperative frozen sections? Asian Pac J Cancer Prev, 14, 6121-5.
  3. Bansal N, Yendluri V, Wenham RM (2009). The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies, cancer control J Moffitt Cancer Center, 16, 8.
  4. Cetinkaya K, Atalay F, Bacinoglu A (2014). Risk factors of lymph node metastases with endometrial carcinoma Asian Pac J Cancer Prev, 15, 6353.
  5. Clifford SC, Astuti D, Hooper L, et al (2001). The pVHLassociated SCF ubiquitin ligase complex: molecular genetic analysis of elongin B and C, Rbx1 and HIF-1alpha in renal cell carcinoma, Oncogene, 20, 5067-74.
  6. Epstein AC, Gleadle JM, McNeill LA, et al (2001). C elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation Cell, 107, 43-54.
  7. Fader AN, Arriba LN, Frasure HE, von Gruenigen VE (2009). Endometrial cancer and obesity: epidemiology, biomarkers, prevention and survivorship, Gynecol Oncol, 114, 121-7.
  8. Garcia-Dios DA, Lambrechts D, Coenegrachts L, et al (2013). High-throughput interrogation of PIK3CA, PTEN, KRAS, FBXW7 and TP53 mutations in primary endometrial carcinoma Gynecol Oncol, 128, 327-34.
  9. Hebert C, Norris K, Parashar P, et al (2006). Hypoxia-inducible factor-1${\alpha}$ polymorphisms and TSC1/2 mutations are complementary in head and neck cancers Molecular Cancer, 5, 3.
  10. Hurwitz H, Fehrenbacher L, Novotny W, et al (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer New England J Med, 350, 2335-42.
  11. Jiang XF, Tang QL, Zou Y, et al (2014). Does HBV infection increase risk of endometrial carcinoma? Asian Pac J Cancer Prev, 15, 713-6.
  12. Kung AL, Klco JM, Kaelin WG, Livingston DM (2000). Suppression of tumor growth through disruption of hypoxiainducible transcription, Nature Med, 6, 1335-40.
  13. Ling TS, Shi RH, Zhang GX, et al (2005). Common single nucleotide polymorphism of hypoxia-inducible factor-1${\alpha}$ and its impact on the clinicopathological features of esophageal squamous cell carcinoma Chinese J Digestive Diseases, 6, 155-8.
  14. Liu FS (2007). Molecular carcinogenesis of endometrial cancer Taiwanese J Obstet Gynecol, 46, 26-32.
  15. Mazurek A, Kuc P (2005). Angiogenesis-prognostic factor in patients with endometrial cancer Ginekologia Polska, 76, 838-45
  16. Minaguchi T, Yoshikawa H, Oda K, et al (2001). PTEN mutation located only outside exons 5, 6, and 7 is an independent predictor of favorable survival in endometrial carcinomas Clinical Cancer Res, 7, 2636-42.
  17. Myatt SS, Wang J, Monteiro LJ, et al (2010). Definition of microRNAs that repress expression of the tumor suppressor gene FOXO1 in endometrial cancer Cancer Res, 70, 367-77.
  18. Neubauer NL, Lurain JR (2011). The role of lymphadenectomy in surgical staging of endometrial cancer. Internl J Surg Oncol, 2011, 814649.
  19. Okuda T, Sekizawa A, Purwosunu Y, et al (2010). Genetics of endometrial cancers. Obstet Gynecol Internl.
  20. Prat J, Gallardo A, Cuatrecasas M, Catasus L (2007). Endometrial carcinoma: pathology and genetics. Pathology, 39, 72-87.
  21. Rasila K, Burger R, Smith H, Lee F, Verschraegen C (2005). Angiogenesis in gynecological oncology-mechanism of tumor progression and therapeutic targets. Internl J Gynecol Cancer, 15, 710-26.
  22. Sun H, Enomoto T, Fujita M, et al (2001). Mutational analysis of the PTEN gene in endometrial carcinoma and hyperplasia. Am J Clin Pathol, 115, 32-8.
  23. Tanimoto K, Yoshiga K, Eguchi H, et al (2003). Hypoxiainducible factor-1${\alpha}$ polymorphisms associated with enhanced transactivation capacity, implying clinical significance. Carcinogenesis, 24, 1779-83.
  24. Thanapprapasr D, Thanapprapasr K (2013). Molecular therapy as a future strategy in endometrial cancer. Asian Pac J Cancer Prev, 14, 3419-23.
  25. Wang HL, Liu MM, Ma X, et al (2014). Expression and effects of JMJD2A histone demethylase in endometrial carcinoma. Asian Pac J Cancer Prev, 15, 3051.
  26. Zeng YW, Yang JZ, Pu XY, et al (2013). Strategies of functional food for cancer prevention in human beings. Asian Pac J Cancer Prev, 14, 1585-92.
  27. Zhao T, Lv J, Zhao J, Nzekebaloudou M (2009). Hypoxiainducible factor-1${\alpha}$ gene polymorphisms and cancer risk: a meta-analysis. J Experimental Clin Cancer Res, 28, 159.
  28. Zhu XL, Ai ZH, Wang J, et al (2012). Weighted gene coexpression network analysis in identification of endometrial cancer prognosis markers. Asian Pac J Cancer Prev, 13, 4607-11.