Association Between Single Nucleotide Polymorphism rs113488022 of BRAF and Endometriosis in Iranian Population

Document Type: Original Article

Authors

1 Department of Molecular and Cellular Sciences, Faculty of Advanced Sciences & Technology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran

2 Department of Molecular Biology and Genetic Science, Faculty of Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.

3 Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Department of Biology, Islamic Azad University Tehran Science and Research Branch, Tehran, Iran.

Abstract

Endometriosis is a benign gynecologic disorder that has malignant-like characteristics such as invasion, and it can cause malignancy and cancer in advanced stages. Genetic, epigenetic and environmental factors play significant roles in the establishment and maintenance of endometriosis. Studies have demonstrated that proto-oncogenes may be an important regulator of cell proliferation in endometriotic tissue. B-Raf is a proto-oncogene, which participates in the MAP kinase/ERK signaling pathway and plays an important role in different types of cancers and disorders. The aim of the present study was to evaluate the association of BRAF gene single nucleotide polymorphism (SNP), rs113488022, with the risk of endometriosis in Iranian women, in order to identify a potential biomarker for the early non-invasive detection of endometriosis and endometriosis-related cancers.
In a population based case-control study conducted in Tehran, in-person interviews were completed for 65 women aged 15– 49 years and an equal number of controls frequency-matched to cases by age. All cases were newly diagnosed with endometriosis and all controls were with no laparoscopic evidence of disease. The genomic DNA was extracted from peripheral blood leucocytes and subsequently the rs113488022 SNP of the BRAF gene was genotyped using amplification refractory mutation system- polymerase chain reaction (ARMS-PCR). Statistical analysis was performed using SPSS. In comparison of case and control groups, no significant differences were found in genotype and allele frequencies. Moreover, the results showed that there was no significant association between the presence of risk allele (A) and increased risk of endometriosis (Odds ratio=0.781, 95% CI: 0.480 -1.272, P=0.321).
In conclusion, there was no evidence of an association between the rs113488022 SNP of the BRAF gene, and overall risk of endometriosis in Iranian population.  Larger studies with different ethnics are needed to validate our findings.

Keywords

References

 

  1. Hiroshi Kobayashi, Shogo Imanaka, Haruki Nakamura,  Ayumi Tsuji. (2014). Understanding the role of  epigenomic,  genomic and genetic alterations in the development of endometriosis (Review). Molecular Medicine Reports, 1483-1505.
  2. Burney RO, Giudice LC. (2012). Pathogenesis and pathophysiology of endometriosis. Fertil. Steril.( 98), 511–519.   
  3. Maryam sadat Hoseini , Ahmad Ebrahimi.  (2017). Detection of HER-2 gene copy number variations as a molecular marker in the peripheral blood of women with endometriosis in Iranian population: Case-control study. Meta Gene. ( 11 ),164–168.
  4. Ivo Brosens, Jan J. Brosens, Giuseppe Benagiano .(2012). The eutopic endometrium in endometriosis: are the changes of clinical significance?. Reproductive BioMedicine Online, 24 (5), 496-502.
  5. Falconer H, D'Hooghe T, Fried G. (2007).  Endometriosis and genetic polymorphisms. Obstet Gynecol Surv, (9),  616-28.
  6. Haiyuan  Liu , Jing He Lang. (2011). Is abnormal eutopic endometrium the cause of endometriosis? The role of eutopic endometrium in pathogenesis of endometriosis. Med Sci Monit, (4), RA92–RA99.
  7. Stefansson H, Geirsson RT, Steinthorsdottir V, Jonsson H. (2002). Genetic factors contribute to the risk of developing endometriosis .Hum Reprod, (3), 555-9.
  8. Treloar SA, O'Connor DT, O'Connor VM, Martin NG. (1999). Genetic influences on endometriosis in an Australian twin sample. Fertil Steril, (4),  701-10.
  9. Li Y, Hao N, Wang YX, Kang S. (2017). Association of Endometriosis-Associated Genetic Polymorphisms From Genome-Wide Association Studies With Ovarian Endometriosis in a Chinese Population. Reprod Sci, (1), 109-113.
  10. Stefanie Burghaus, Lothar Häberle, Michael G. Schrauder, Katharina Heusinger. ( 2015). Endometriosis as a risk factor for ovarian or endometrial cancer—results of a hospital-based case–control study. BMC Cancer, (15), 751.
  11. Chen Q, Zhang C, Chen Y, Lou J, Wang D.( 2012). Identification of endometriosis-related genes by representational difference analysis of cDNA. Obstet Gynaecol, (2),140-5.
  12. Xiao Lv, Danbo Wang, Yue Ma, Zaiqiu Long. (2018).  Analysis of the oncogene BRAF mutation and the correlation of the expression of wild-type BRAF and CREB1 in endometriosis. Int J Mol Med, (3),1349-1356.
  13. Muhammad Ramzan Manwar Hussain, Mukhtiar Baig, Hussein Sheik Ali Mohamoud, Zaheer Ulhaq. (2015).  BRAF gene: From human cancers to developmental syndromes .Saudi J Biol Sci,  22(4),  359–373.
  14. Sadlecki P, Walentowicz P, Bodnar M, Marszalek A. (2017). Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers. Tumour Biol, (5), 1010428317706230.
  15. Grace W. Weyant, Jeffrey D. Wisotzkey, Floyd A. Benko, Keri J. Donaldson. (2014). BRAF mutation testing in solid tumors: a methodological comparison. J Mol Diagn, (5), 481-5.
  16. Kyaw L. Aung, Emma Donald, Gillian Ellison, Sarah Bujac. (2014). Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System. J Mol Diagn, 16(3), 343-9.
  17. Uiju Cho, Woo Jin Oh, Ja Seong Bae, Sohee Lee , Chan Kwon Jung. (2014). Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients. J Korean Med Sci, 29(8), 1054–1060.
  18. Alexander M. Metcalf, Amanda B. Spurdle. (2014). Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review. Fam Cancer, 13(1), 1-12.
  19. Anne L. Estep, Chana Palmer, Frank McCormick, Katherine A. Rauen . (2007). Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines: implications for therapy. PLoS One, 2(12),  e1279.
  20. Yu-Zhen Feng, Tanri Shiozawa, Tsutomu Miyamoto, Hiroyasu Kashima. (2005). BRAF mutation in endometrial carcinoma and hyperplasia: correlation with KRAS and p53 mutations and mismatch repair protein expression. Clin Cancer Res, 11(17),  6133-8.
  21. Robertson Mackenzie, Stefan Kommoss,  Boris J. Winterhoff, Benjamin R. Kipp.(2015)  .Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms. BMC Cancer, 15:415.
  22. Farr Nezhat, M. Shoma Datta, Veneta Hanson, Tanja Pejovic. (2008). The relationship of endometriosis and ovarian malignancy: a review. Fertil  Steril, (90), 1559–1570.
  23. Qi Chen , ChiYuan Zhang,  YingHan Chen,   Jie Lou,  DanBo Wang. (2012). Identification of endometriosis‐related genes by representational difference analysis of cDNA. Australian and New Zealand Journal of Obstetrics and Gynaecology ,(52  ),140-145.
  24. Anna L. Vestergaard,  Katrine Thorup,  Ulla B. Knudsen,  Torben Munk. (2011). Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis. Mol Hum Reprod,  (17), 758–761.
Journal of Tissues and Materials

Volume 1, Issue 1
Autumn 2018
Pages 25-31

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History

  • Receive Date: 01 June 2018
  • Revise Date: 15 June 2018
  • Accept Date: 14 July 2018

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