The association between KRAS gene expression and breast tumors in a sample of Iraqi women

The association between KRAS gene expression and breast tumors in a sample of Iraqi women

In Iraq, breast cancer is considered one of the most widespread cancer types causing death in women due to changes in the genes that control cell growth and proliferation. KRAS gene plays a role in 30% of human cancers. This study aims to evaluate the expression of the KRAS gene and its role in women with breast tumours. A total of 120 women (60 women with breast tumours and 60 samples from apparently healthy women) were enrolled in this study to determine the expression of the KRAS gene. The RT-qPCR was used for this purpose. Fibroadenoma (FA) was the most common tumours, accounting for 53% of cases, followed by fibrocystic change (26%). Other benign tumours accounted for 20% of the cases; however, IDC is the most common type of invasive breast cancer, accounting for 70% of all breast cancers. Moreover, KRAS gene expression in women with breast tumours (benign and malignant) was not- significantly different from that seen in normal healthy women.

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  • 1. Lukasiewicz, S., Czeczelewski , M., Forma, A., Baj, J., Sitarz, R. and Stanisławek, A., “Breast Cancer—Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies—An Updated Review”. Cancers 2021 (13): 4287.
  • 2. Sung, H., Ferlay, J., Siegel, R. L.; Laversanne, M.; Soerjomataram, I., Jemal, A., Bray, F., “Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries”. CA Cancer J Clin 2021;71:209–249.
  • 3. Iraqi Cancer Board, “Results of the Iraqi Cancer Registry 2019”. Baghdad, Iraqi Cancer Registry Center, Ministry of Health. 2019.
  • 4. kontomanolis, E., koutras, A., syllaios, A., schizas, D., mastoraki,A., garmpis,N., diakosavvas,D., angelou,K., tsatsaris, G., pagkalos,A., ntounis, T.,and fasoulakis.Z., “Role of Oncogenes and Tumor-suppressor Genes in Carcinogenesis: A Review”. Anticancer research 40 2020: 6009-6015.
  • 5. Dobre, M.; Dinu, D.; Panaitescu, E.; Bîrlă, R.; Iosif, C. et al.,“KRAS Gene Mutations-Prognostic Factor in Colorectal Cancer. Rom”. J. Morphol. Embryol 2015. 56(2):671–78. 6. Galiè, M. “RAS as Supporting Actor in Breast Cancer”. Front. Oncol. 2019. 9:1199
  • 7. Smits, K., Paranjape T., Nallur S., Wouters, K., Weijenberg, M., Schouten, L., Brandt, P., Bosman, F. T., Weidhaas, J. B., and Engeland, M. “A let-7 microRNA SNP in the KRAS 3'UTR is prognostic in early-stage colorectal Cancer”. Clin. Cancer Res 2011.; 17 (24):7723±7731. 8. Kim, M., Kogan, N. and Slack, F. “Cis-acting elements in its 3′ UTR mediate post-transcriptional regulation of KRAS”. Oncotarget 2016. 7(11).
  • 9. Karnoub, A., Weinberg, R. “Ras oncogenes: split personalities”. Nat Rev Mol Cell Biol 2008; 9(7):517± 531.
  • 10. Yang, M.; Xiao, X.; Xing, X.; Li, X.; Xia, T. et al. “KRAS and VEGF Gene 3’-UTR Single Nucleotide Polymorphisms Predicted Susceptibility in Colorectal Cancer”. PLOS ONE. .2017.12(3):e0174140
  • 11. Bruno, A.; Li, L.; Kalabus, J.; Pan, Y.; Yu, A. and Hu, Z. “miRdSNP: A Database of Disease-Associated SNPs and microRNA Target Sites on 3’- UTRs of Human Genes”. BMC Genomics .2012. 13(44):1–7
  • 12. Yang, Z. and Liu, Z. “The Emerging Role of MicroRNAs in Breast Cancer”. J. of Oncology 2020. 1-7.
  • 13. Grechukhina, O.; Petracco, R.; Popkhadze, S.; Massasa, E.; Paranjape, T. et al. “A Polymorphism in a Let-7 microRNA Binding Site of KRAS in Women with Endometriosis”. EMBO Molecular Medicine 2012. 4(3):206–17.
  • 14. Stephenson, F. “Calculations for Molecular Biology and Biotechnology A guide to Mathematics in Laboratory”. 2nd edition. Elsevier Inc.2010 15. Hwang , K., Kim , B., Oh, S., Park , S., Jung, J., Kim, J., Choi, I., Jeon, S., Kim, W. “Prognostic Role of KRAS mRNA Expression in Breast Cancer”. J Breast Cancer. .2019: 22(4):548-561
  • 16. Deng, N., Zhou, H., Fan, H., and Yuan, Y. Single nucleotide polymorphisms and cancer susceptibility. Oncotarget 2017, 8:110635-110649
  • 17. Chin, L .; Ratner, E.; Leng, S.; Zhai, R.; Nallur, S. et al.“ A SNP in a Let-7 microrna Complimentary Site in the KRAS 3′UTR Increases Non-Small Cell Lung Cancer Risk”. Cancer Res. 2008, 68(20):8535–40.
  • 18. Al-Haddad, R., Jasim, H., Saleh, W. “Lack of Association between LCS6 Variant in KRAS Gene with the Occurrence of Breast Tumors in Iraqi Women”. Baghdad Sci J. 2020.17(2):426-430.
  • 19. Baek, D.; Villen, J.; Shin, C.; Camargo, F.D.; Gygi, S.P. et al. “The impact of micrornas on protein output”. Nature2008 .455: 64–71.
  • 20. Kim, M. and Slack, F.J. “Microrna-Mediated Regulation of KRAS in Cancer”. Journal of Hematology & Oncology 2014.7(84):1–4.
  • 21. Zhou, C.; Lu, Y. and Li, X. “miR-339-3p inhibits proliferation and metastasis of colorectal cancer”. Oncol Lett. 2015.10(5):2842.
  • 22. Hatley, M.E.; Patrick, D.M.; Garcia, M.R.; Richardson, J.A., Bassel- Duby, R., van Rooij, E. et al., “Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21”. Cancer Cell. .2010 .18: 282–293.
  • 23. Shin, K.; Bae, S.; Hong, H., Kim, R.; Kang, M. et al., “Mir-181a Shows Tumor Suppressive Effect against Oral Squamous Cell Carcinoma Cells by Downregulating K-Ras”. Biochemical and Biophysical Research Communications. 2011. 404(4):896–902.
  • 24. Tanic, M.; Yanowsky, K.; Rodriguez-Antona, C.; Andrés, R.; Márquez- Rodas, I. et al., “Deregulated mirnas in Hereditary Breast Cancer Revealed a Role for mir-30c in Regulating KRAS Oncogene”. Plos one . 2012. 7(6):e38847
  • 25. You, C.; Liang, H.; Sun, W.; Li, J.; Liu, Y. et al.“ Deregulation of the miR-16-KRAS axis promotes colorectal cancer”. Sci Rep.2016, 6: 37459.