DOI QR코드

DOI QR Code

Evaluation of KRAS Gene Mutations in Metastatic Colorectal Cancer Patients in Kermanshah Province

  • Amirifard, Nasrin (Cancer Research Center, Kermanshah University of Medical Sciences) ;
  • Sadeghi, Edris (Cancer Research Center, Kermanshah University of Medical Sciences) ;
  • Farshchian, Negin (Cancer Research Center, Kermanshah University of Medical Sciences) ;
  • Haghparast, Abbas (Medical Physics Department, Faculty of Medicine, Kermanshah University of Medical Sciences) ;
  • Choubsaz, Mansour (Cancer Research Center, Kermanshah University of Medical Sciences)
  • Published : 2016.07.01

Abstract

Background: Worldwide, colorectal cancer (CRC) is reported to be the fourth most common cancer in men and the third most common in women. KRAS is a proto-oncogene located on the short arm of chromosome 12. The aim of this study was to evaluate the KRAS oncogene and its relationship it with clinicopathologic features in 33 Kurdish patients. Materials and Methods: Metastatic CRC between 2012 and 2016 that came to Imam Reza hospital, Kermanshah province, Iran, were analysed for KRAS mutations using allele specific PCR primers and pyrosequencing. Correlations between variables was analyzed in PASW SPSS and overall survival curves were plotted in Graph Pad prism 5. Results: The mean age for them at diagnosis was $51.5{\pm}12.6$ years (range, 22-76 years). Among the 33 patients that were sequenced, 12 samples in the KRAS gene had a nucleotide change, 11 in codon 12 and 1 in codon 13.There was no significant relationship between the mutation and clinical and pathological aspects of the disease. Conclusions: Knowledge of the KRAS status can help in decision-making to treat metastatic colorectal cancer patients more efficiently and increase survival. However, many Kurdish people due to economic problems are not able to do this valuable genetic test. In addition, we need more careful research of KRAS oncogene at the molecular level in young populations with more patients.

Keywords

Colorectal cancer;KRAS;mutation;PCR;wild type

References

  1. Madani SH, Sadeghi E, Rezaee A, et al (2015). Survey of HER2-neu expression in colonic adenocarcinoma in the west of Iran. Asian Pac J Cancer Prev, 16, 7671-4. https://doi.org/10.7314/APJCP.2015.16.17.7671
  2. Carethers JM (2015). Biomarker-directed targeted therapy in colorectal cancer. J Dig Cancer Rep, 3, 5-10.
  3. Vecchione L, Jacobs B, Normanno N, et al (2011). EGFR-targeted therapy. Exp Cell Res, 317, 2765-71. https://doi.org/10.1016/j.yexcr.2011.08.021
  4. Bando H, Yoshino T, Tsuchihara K, et al (2011). KRAS mutations detected by the amplification refractory mutation system-Scorpion assays strongly correlate with therapeutic effect of cetuximab. Br J Cancer, 105, 403-6. https://doi.org/10.1038/bjc.2011.247
  5. Van Cutsem E, Kohne CH, Hitre E, et al (2009). Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med, 360, 1408-17. https://doi.org/10.1056/NEJMoa0805019
  6. Dobre M, Dinu DE, Panaitescu E, et al (2015). KRAS gene mutations - prognostic factor in colorectal cancer? Rom J Morphol Embryol, 56, 671-8.
  7. Perkins G, Pilati C, Blons H, et al (2014). Beyond KRAS status and response to anti-EGFRtherapy in metastatic colorectal cancer. Pharmacogenomics, 15, 1043-52. https://doi.org/10.2217/pgs.14.66
  8. Rosty C, Young JP, Walsh MD, et al (2013). Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features. Mod Pathol, 26, 825-34. https://doi.org/10.1038/modpathol.2012.240
  9. Yoon HH, Tougeron D, Shi Q, et al (2014). KRAS codon 12 and13 mutations in relation to disease-free survival in BRAF-wild-type stage III colon cancers from an adjuvant chemotherapy trial (N0147 alliance). Clin Cancer Res,20, 3033-43. https://doi.org/10.1158/1078-0432.CCR-13-3140
  10. Sameen S, Barbuti R, Milazzo P, et al (2016). Mathematical modeling of drug resistance due to KRAS mutation in colorectal cancer. J Theor Bio, 389, 263-73. https://doi.org/10.1016/j.jtbi.2015.10.019
  11. Chang YY, Lin JK, Lin TC, et al (2014). Impact of KRAS mutation on outcome of patients with metastatic colorectal cancer. Hepatogastroenterol, 61, 1946-53.
  12. Dobre M, Comanescu M, Arsene D, et al (2013). K-ras gene mutation status in colorectal cancer: comparative analysis of pyrosequencing and PCR-RFLP. Rom J Morphol Embryol, 54, 567-74.
  13. Dobre M, Dinu DE, Panaitescu E, et al (2015).KRAS gene mutations - prognostic factor in colorectal cancer? Rom J Morphol Embryol, 56, 671-8.
  14. Faghani M, FakhriehAsl S, Mansour-Ghanaei F, et al (2012). The Correlation between Microsatellite Instability and the Features of Sporadic Colorectal Cancer in the North Part of Iran. Gastroenterol Res Pract, 2012, 756263.
  15. Geramizadeh B (2015). Molecular Biomarkers of Colorectal Cancer: A Review of Published Articles From Iran. Ann Colorectal Res, 3, 30100.
  16. Ansari R, Amjadi H, NorozbeigiN, et al (2007).Survival analysisof colorectal cancer in patients underwent surgical operationin Shariati and Mehr Hospital-Tehran, in a retrospective study. Govaresh, 12, 7-15.
  17. Naghibalhossaini F, Hosseini HM, Mokarram P, et al (2011). High frequency of genes' promoter methylation, butlack of BRAF V600E Mutation among Iranian colorectal cancerpatients. Pathol Oncol Res, 17, 819-25. https://doi.org/10.1007/s12253-011-9388-5
  18. Li FH, Shen L, Li ZH, Luo HY, et al (2010).Impact of KRAS mutation and PTEN expression on cetuximab-treated colorectal cancer. World J Gastroenterol, 16, 5881-88. https://doi.org/10.3748/wjg.v16.i46.5881
  19. Mao C, Zhou J, Yang Z, et al (2012). KRAS, BRAF and PIK3CAmutations and the loss of PTEN expression in Chinese patients with colorectal cancer. PLoS One, 7, 36653. https://doi.org/10.1371/journal.pone.0036653
  20. Nakanishi R, Harada J, Tuul M, et al (2013).Prognostic relevance of KRASandBRAFmutations in japanese patients with colorectal cancer. Int J ClinOncol, 18, 1042-48.
  21. Zlobec I, Bihl MP, Schwarb H, et al (2010). Clinicopathological and protein characterization of BRAF-and K-RAS-mutated colorectal cancer and implications for prognosis. Intl J Cancer, 127, 367-80.
  22. Chaiyapan W, Duangpakdee P, Boonpipattanapong T, et al (2013).Somatic mutations of K-ras and BRAF in Thai colorectal cancer and their prognostic value. Asian Pac J Cancer Prev, 14, 329-32. https://doi.org/10.7314/APJCP.2013.14.1.329