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Molecular Biomarkers of Colorectal Cancer: A Review of Published Articles From Iran

1 Department of Pathology, Transplant Research Center, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, IR Iran
*Corresponding author: Bita Geramizadeh, Department of Pathology, Transplant Research Center, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, IR Iran. Tel/Fax: +98-7136683664, E-mail:
Annals of Colorectal Research. 3(3): e30100 , DOI: 10.17795/acr-30100
Article Type: Review Article; Received: May 19, 2015; Revised: Jul 1, 2015; Accepted: Jul 3, 2015; epub: Oct 9, 2015; collection: Oct 2015


Context: Colorectal cancer is one of the most common cancers worldwide (the third most common cancer in the world) and is especially more common in Western countries; however, its incidence has been increased significantly during the last few years in Eastern countries such as Iran and considered as one of the five common cancers in this country. According to molecular pathways, numerous biomarkers have been identified for colorectal cancers which help patients’ management.

Evidence aquisition: In this study, we tried to review published articles about the molecular biomarkers of colorectal cancer from Iran. We searched medical databases such as google scholar, Scopus, PubMed, Magiran, SID and Iran Medex for keywords of “colon cancer, KRAS, BRAF, mismatch repair gene, Microsatellite instability, molecular genetics, molecular pathogenesis, biomarker and Iran” to find studies published about colorectal cancers from Iran regarding molecular biomarkers.

Conclusion: This study showed that molecular biomarkers in colorectal cancer of Iranian patients are not so different from Western population.

Keywords: Biological Markers; Colorectal Cancer; Cancer

1. Introduction

Colorectal cancer is one of the most common cancers worldwide (the third most common cancer in the world), and is especially more common in Western countries; however, its incidence has been increased significantly during the last few years in Eastern countries such as Iran and considered as one of the five common cancers in this country (1). According to the annual reports of the Cancer Institute, colorectal cancer is the third common cancer in Iranian women and the fifth common cancer in Iranian men. Incidence rate of the disease has been increased during the past 25 years in Iran (2).

The other important finding about this cancer is significant surge of incidence in younger age population compared to older population (3). The underlying cause of this epidemiological increase can be due to changing in lifestyle and environmental factors; however, familial clustering and genetic predisposition should be considered (4). Colorectal cancers can be sporadic, familial and hereditary. HNPCC (hereditary nonpolyposis colon cancer) or Lynch syndrome is the most common form of hereditary colorectal cancer accounting for 5 - 10% of entire colorectal cancer population. Based on previous studies in Iran, clinical diagnosis of HNPCC was observed in 4.7% of probands in Tehran (5).

Molecular pathogenesis of colorectal cancer has been extensively studied and its molecular carcinogenesis has been identified far more than any other cancer. Recent advances in molecular biomarkers to personalize therapy contributed to a major progress in the treatment and prognosis of the disease (6). Many of these molecular changes and biomarkers are now a part of routine laboratory tests and some would be in the near future.

There are several molecular pathways leading to colon cancer. The three most important recognized pathways are 1) Genomic instability which can be somatic and germ line; several forms of genomic instability are chromosomal instability in tumor suppressor genes such as SMAD-4, TP53 and APC (Adenomatous polyposis gene); DNA repair defects (in mismatch repair genes) and aberrant DNA methylation are two other patterns of chromosomal instability; 2) Mutational inactivation of tumor suppressor genes mostly in APC (adenomatous polyposis gene), TP53, TGF-β tumor suppressor pathway, and mismatch repair genes (MMR) and 3) Activation of oncogenic pathways of RAS, BRAF, Phosphatidyl inositol 3-kinase (PIK-3) (7).

According to these molecular pathways, numerous biomarkers have been identified for colorectal cancers to help patients’ management (8). In this study, we tried to review published articles about the molecular biomarkers of colorectal cancer from Iran. We searched medical databases such as google scholar, Scopus, PubMed, Magiran, SID and Iran medex for keywords “colon cancer, KRAS, BRAF, mismatch repair gene, Microsatellite instability, molecular genetics, molecular pathogenesis, biomarker and Iran” to find studies published about the colorectal cancers from Iran regarding molecular biomarkers.

3. KRAS Mutation

Management of metastatic colorectal carcinoma (mCRC) has been considerably improved after discovering a number of novel drugs, including targeted agents like bevacizumab, cetuximab, and panitumumab. The overall survival of advanced disease has been considerably improved by adding newer targeted biologic agents. In the recent years, more studies have been focused on selecting patients who would benefit from these targeted therapies. This focuses on the role of the KRAS mutation in the growth and histopathology of the tumor, clinical outcomes and management choice of cancer of the large bowel (19, 20). This proto-oncogene, KRAS, is regularly mutated (30 - 50% in different surveys) in CRC. Roughly, 90% of the activating mutations that are influential solitary amino acid replacement in the GTPase pocket and guide a block of the activity of KRAS-p21 protein, are recognized in codons 12 (GGT) and 13 (GGC) of exon 1 and almost 5% in codon 61 (CAA) situated in exon 2. The most regularly found kinds of mutations are G > A and G > T transitions (21). KRAS testing has a vital improvement in the treatment of CRCs, especially after metastasis (19, 20, 22). There are very few studies about the frequency of K-ras mutation from the Middle East and Iran; consequently, in the present study, we reviewed KRAS mutation rate and spectrum in previous studies from Iran.

As Table 2 shows, the prevalence of KRAS mutation in Iran is similar to studies from other countries; the overall reported prevalence from different countries have been as low as 20 to 50%, and in the few studies from Iran, this was 12.5% - 37.4% (29-32). The most common KRAS mutation in most previous studies has been 12G - A, and in one study from south of Iran was 12 G - C (29-32).

Table 2.
Reported KRAS Mutation in Previous Studies on Iranian Population

4. BRAF Mutation

BRAF is the last discovered member of RAF family proteins in MAPKinase signaling pathway, which acts with KRAS as a downstream serine threonine kinase effector downstream to epidermal growth factor receptor (EGFR), promoting cell proliferation (33). The most prevalent mutation in the BRAF gene in all cancers involves transversion of thymidine to adenosine at nucleotide position 1799 of exon 15, leading to conversion of GTG codon (Valine) to GAG (Glutamic acid), labeled as V600E, accounting for more than 90% of the observed mutations in this gene (33, 34). V600E BRAF gene mutation is associated with older age, female gender, proximal colon location, poor differentiation, mucinous histology, infiltrating lymphocytes and advanced stage (35, 36). BRAF mutations occur more frequently in MSI and CIMP-H (Cpg island methylator phenotype-high) CRCs and only rarely with MSS CRCs and mutually exclusive with KRAS mutations (35-37). BRAF seems to be an independent negative prognostic factor in CRCs (38, 39). In some studies, BRAF gene mutation analysis has been suggested for exclusion of HNPCC Syndrome (40, 41). Two monoclonal antibodies, Cetuximab and Panitumumab, target EGFR, and have been approved to treat metastatic CRC (42). Analysis of mutational status of the BRAF gene is recommended before initiating these new targeted therapies in metastatic CRC patients (42, 43). Most previous reports from different parts of the world showed that frequency of BRAF gene mutation is usually low. The frequency of BRAF mutation has been reported as low as zero in Thailand (44) and Mexico (45) to 12.2% in Australia (46). Studies from Western countries such as the USA (United States of America) reported the prevalence of about 9% - 10% (47). There are very few studies from Iran. Table 3 shows previous studies from Iran with BRAF mutation prevalence from 0 to 3.7% (18, 30, 48, 49).

Table 3.
Reported BRAF Mutation in the Previous Studies in Iranian Population

5. P53

TP53 is the pivotal mediator of growth arrest and apoptosis in response to DNA damage. It stops cell cycle in damaged cells until alteration is properly repaired, otherwise it starts apoptosis cascade in damaged cells. Human P53 gene is composed of 11 exons and codes a protein with 393 amino acids (50). About 13 types of polymorphisms have been described in this gene (51). These polymorphisms can affect colorectal cancer risk, prognosis and response to treatment (52, 53).

There are about 9 studies from Iran regarding different roles of P53 gene in colorectal cancer. One of the most frequent studied polymorphism has been in codon 72, exon 4. The studies regarding this polymorphism have shown that different people with different genotypes in this codon can have more risk of developing colorectal cancer in patients from Iran (54-56). There are also reports about the prognosis and response to specific treatment in patients with some mutations in exons 4, 5 and 6 (57, 58). This biomarker is still not a part of recommended biomarker panel for patients with colorectal cancers; however, some studies recommended evaluation of specific mutational analysis in P53 to predict response to treatment and prognosis (59).

6. Other Biomarkers in Colorectal Cancer

In addition to the above mentioned most common and important molecular biomarkers of colorectal cancer, there are other studies regarding less common and known biomarkers in colorectal cancer of Iranian patients in both genes of hereditary cancers such as APC (adenomatous polyposis coli) gene and sporadic CRCs such as Smad-7, EGF (epidermal growth factor) and MGMT (O 6- ethylguanine-DNA methyltransferase) (60-63). There are very few studies in Iranian population regarding these newly recommended biomarkers such as NRAS and PIK3CA to be the source of decision about prognosis or risk of CRC in Iranian patients with this cancer.

7. Conclusions

CRC is one of the most common cancers in Iranian population, which emphasizes the need to find better methods to screen, diagnose and treat patients with this cancer. Molecular biomarkers can help in prediction of the risk of CRC in people, early diagnosis of this cancer, treat patients more efficiently and safely and at last increase the survival of patients with this cancer.


  • 1. Kolahdoozan S, Sadjadi A, Radmard AR, Khademi H. Five common cancers in Iran. Arch Iran Med. 2010;13(2):143-6. [PubMed]
  • 2. Mohammadianpanah M. Characteristics of the patients with colorectal cancer: epidemiologic study or pathology report-based study. Iran Red Crescent Med J. 2015;17(1):eee17899 [DOI] [PubMed]
  • 3. Malekzadeh R, Bishehsari F, Mahdavinia M, Ansari R. Epidemiology and molecular genetics of colorectal cancer in iran: a review. Arch Iran Med. 2009;12(2):161-9. [PubMed]
  • 4. Mehrabani D, Tabei S, Heydari S, Shamsina S, Shokrpour N, Amini M, et al. Cancer Occurrence in Fars Province, Southern Iran. Iran Red Crescent Med J. 2008;10(4):314-22.
  • 5. Akrami SM. Genetics of hereditary nonpolyposis colorectal cancer. Arch Iran Med. 2006;9(4):381-9. [PubMed]
  • 6. Masoompour SM, Yarmohammadi H, Rezaianzadeh A, Lankarani KB. Cancer incidence in southern Iran, 1998-2002: results of population-based cancer registry. Cancer Epidemiol. 2011;35(5):e42-7. [DOI] [PubMed]
  • 7. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med. 2009;361(25):2449-60. [DOI] [PubMed]
  • 8. Zamanian-Azodi M, Rezaei-Tavirani M, Hasanzadeh H, Rahmati Rad S, Dalilan S. Introducing biomarker panel in esophageal, gastric, and colon cancers; a proteomic approach. Gastroenterol Hepatol Bed Bench. 2015;8(1):6-18. [PubMed]
  • 9. Shemirani AI, Haghighi MM, Zadeh SM, Fatemi SR, Taleghani MY, Zali N, et al. Simplified MSI marker panel for diagnosis of colorectal cancer. Asian Pac J Cancer Prev. 2011;12(8):2101-4. [PubMed]
  • 10. Mokarram P, Rismanchi M, Alizadeh Naeeni M, Mirab Samiee S, Paryan M, Alipour A, et al. Microsatellite instability typing in serum and tissue of patients with colorectal cancer: comparing real time PCR with hybridization probe and high-performance liquid chromatography. Mol Biol Rep. 2014;41(5):2835-44. [DOI] [PubMed]
  • 11. Shahmoradi S, Bidmeshkipour A, Salamian A, Emami MH, Kazemi Z, Salehi M. Two novel mutations in hMLH1 gene in Iranian hereditary non-polyposis colorectal cancer patients. Fam Cancer. 2012;11(1):13-7. [DOI] [PubMed]
  • 12. Montazer Haghighi M, Radpour R, Aghajani K, Zali N, Molaei M, Zali MR. Four novel germline mutations in the MLH1 and PMS2 mismatch repair genes in patients with hereditary nonpolyposis colorectal cancer. Int J Colorectal Dis. 2009;24(8):885-93. [DOI] [PubMed]
  • 13. Milanizadeh S, Khanyaghma M, Haghighi MM, Mohebbi S, Damavand B, Almasi S, et al. Molecular analysis of imperative polymorphisms of MLH1 gene in sporadic colorectal cancer. Cancer Biomark. 2013;13(6):427-32. [DOI] [PubMed]
  • 14. Molaei M, Mansoori BK, Ghiasi S, Khatami F, Attarian H, Zali M. Colorectal cancer in Iran: immunohistochemical profiles of four mismatch repair proteins. Int J Colorectal Dis. 2010;25(1):63-9. [DOI] [PubMed]
  • 15. Haghighi MM, Aghagolzadeh P, Zadeh SM, Molaei M, Zali MR, Radpour R. Telomere shortening: a biological marker of sporadic colorectal cancer with normal expression of p53 and mismatch repair proteins. Genet Test Mol Biomarkers. 2014;18(4):236-44. [DOI] [PubMed]
  • 16. Bishehsari F, Mahdavinia M, Malekzadeh R, Verginelli F, Catalano T, Sotoudeh M, et al. Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatellite instability status and country of origin. Ann Oncol. 2006;17 Suppl 7:vii91-6. [DOI] [PubMed]
  • 17. Salehi M, Amani S, Javan S, Emami MH, Salamat MR, Daloii MRN. Evaluation of MLH1 and MSH2 gene mutations in a subset of Iranian families with hereditary nonpolyposis colorectal cancer (HNPCC). J Sci Islamic Republic Iran. 2009;20(1):7-12.
  • 18. Brim H, Mokarram P, Naghibalhossaini F, Saberi-Firoozi M, Al-Mandhari M, Al-Mawaly K, et al. Impact of BRAF, MLH1 on the incidence of microsatellite instability high colorectal cancer in populations based study. Mol Cancer. 2008;7:68. [DOI] [PubMed]
  • 19. Haghighi MM, Javadi GR, Parivar K, Milanizadeh S, Zali N, Fatemi SR, et al. Frequent MSI mononucleotide markers for diagnosis of hereditary nonpolyposis colorectal cancer. Asian Pac J Cancer Prev. 2010;11(4):1033-5. [PubMed]
  • 20. Moghbeli M, Moaven O, Dadkhah E, Farzadnia M, Roshan NM, Asadzadeh-Aghdaee H, et al. High frequency of microsatellite instability in sporadic colorectal cancer patients in Iran. Genet Mol Res. 2011;10(4):3520-9. [DOI] [PubMed]
  • 21. Faghani M, Fakhrieh Asl S, Mansour-Ghanaei F, Aminian K, Tarang A, Seighalani R, et al. The Correlation between Microsatellite Instability and the Features of Sporadic Colorectal Cancer in the North Part of Iran. Gastroenterol Res Pract. 2012;2012:756263. [DOI] [PubMed]
  • 22. Brim H, Abu-Asab MS, Nouraie M, Salazar J, Deleo J, Razjouyan H, et al. An integrative CGH, MSI and candidate genes methylation analysis of colorectal tumors. PLoS One. 2014;9(1):eee82185 [DOI] [PubMed]
  • 23. Esmailnia G, Montazer-Haghighi M, Javadi G, Parivar K, Zali M. Microsatellite instability markers status in colorectal cancer. Zahedan J Res Med Sci. 2014;16(12):25-8.
  • 24. Zeinalian M, Emami MH, Naimi A, Salehi R, Hashemzadeh-Chaleshtori M. Immunohistochemical analysis of mismatch repair proteins in Iranian colorectal cancer patients at risk for lynch syndrome. Iran J Cancer Prev. 2015;8(1):7-11. [PubMed]
  • 25. Zeinalian M, Emami MH, Salehi R, Naimi A, Kazemi M, Hashemzadeh-Chaleshtori M. Molecular analysis of Iranian colorectal cancer patients at risk for Lynch syndrome: a new molecular, clinicopathological feature. J Gastrointest Cancer. 2015;46(2):118-25. [DOI] [PubMed]
  • 26. Homayouni V, Salehi M, Kazemi M. Investigating of microsatellites instability in patients with hereditary non-polyposis colorectal cancer in Isfahan. Adv Biomed Res. 2014;3:145. [DOI] [PubMed]
  • 27. Sinicrope FA, Sargent DJ. Clinical implications of microsatellite instability in sporadic colon cancers. Curr Opin Oncol. 2009;21(4):369-73. [DOI] [PubMed]
  • 28. Mokarram P, Kumar K, Brim H, Naghibalhossaini F, Saberi-firoozi M, Nouraie M, et al. Distinct high-profile methylated genes in colorectal cancer. PLoS One. 2009;4(9):eee7012 [DOI] [PubMed]
  • 29. Shemirani AI, Haghighi MM, Milanizadeh S, Taleghani MY, Fatemi SR, Damavand B, et al. The role of kras mutations and MSI status in diagnosis of colorectal cancer. Gastroenterol Hepatol Bed Bench. 2011;4(2):70-2. [DOI] [PubMed]
  • 30. Naghibalhossaini F, Hosseini HM, Mokarram P, Zamani M. High frequency of genes' promoter methylation, but lack of BRAF V600E mutation among Iranian colorectal cancer patients. Pathol Oncol Res. 2011;17(4):819-25. [DOI] [PubMed]
  • 31. Sobhani S, Ghafarpoor SM, Mostakhdemin Hosini Z, Kamali F, Noormohamadi Z, Hooshmand M. Frequency of common mutation in codon 12 and 13 of KRAS in patients with colorectal cancer in Iranian population. Genetic Third Millennium. 2009;8:2011-8.
  • 32. Omidifar N, Geramizadeh B, Mirzai M. KRAS Mutation in Colorectal cancer, a report from South of Iran. IJMS. In press;5(5)
  • 33. Roskoski RJ. RAF protein-serine/threonine kinases: structure and regulation. Biochem Biophys Res Commun. 2010;399(3):313-7. [DOI] [PubMed]
  • 34. Cantwell-Dorris ER, O'Leary JJ, Sheils OM. BRAFV600E: implications for carcinogenesis and molecular therapy. Mol Cancer Ther. 2011;10(3):385-94. [DOI] [PubMed]
  • 35. Li WQ, Kawakami K, Ruszkiewicz A, Bennett G, Moore J, Iacopetta B. BRAF mutations are associated with distinctive clinical, pathological and molecular features of colorectal cancer independently of microsatellite instability status. Mol Cancer. 2006;5:2. [DOI] [PubMed]
  • 36. Tie J, Gibbs P, Lipton L, Christie M, Jorissen RN, Burgess AW, et al. Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF(V600E) mutation. Int J Cancer. 2011;128(9):2075-84. [DOI] [PubMed]
  • 37. Velho S, Moutinho C, Cirnes L, Albuquerque C, Hamelin R, Schmitt F, et al. BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: primary or secondary genetic events in colorectal carcinogenesis? BMC Cancer. 2008;8:255. [DOI] [PubMed]
  • 38. Ogino S, Nosho K, Kirkner GJ, Kawasaki T, Meyerhardt JA, Loda M, et al. CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut. 2009;58(1):90-6. [DOI] [PubMed]
  • 39. Yokota T, Ura T, Shibata N, Takahari D, Shitara K, Nomura M, et al. BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer. Br J Cancer. 2011;104(5):856-62. [DOI] [PubMed]
  • 40. Rasuck CG, Leite SM, Komatsuzaki F, Ferreira AC, Oliveira VC, Gomes KB. Association between methylation in mismatch repair genes, V600E BRAF mutation and microsatellite instability in colorectal cancer patients. Mol Biol Rep. 2012;39(3):2553-60. [DOI] [PubMed]
  • 41. Jensen LH, Dysager L, Lindebjerg J, Kolvra S, Byriel L, Cruger DG. Molecular biology from bench-to-bedside - which colorectal cancer patients should be referred for genetic counselling and risk assessment. Eur J Cancer. 2010;46(10):1823-8. [DOI] [PubMed]
  • 42. Muhammad S, Jiang Z, Liu Z, Kaur K, Wang X. The role of EGFR monoclonal antibodies (MoABs) cetuximab/panitumab, and BRAF inhibitors in BRAF mutated colorectal cancer. J Gastrointest Oncol. 2013;4(1):72-81. [DOI] [PubMed]
  • 43. Katsios C, Ziogas DE, Roukos DH. Colorectal cancer: cetuximab, KRAS, BRAF, PIK3CA mutations and beyond. Expert Rev Gastroenterol Hepatol. 2010;4(5):525-9. [DOI] [PubMed]
  • 44. Chaiyapan W, Duangpakdee P, Boonpipattanapong T, Kanngern S, Sangkhathat S. Somatic mutations of K-ras and BRAF in Thai colorectal cancer and their prognostic value. Asian Pac J Cancer Prev. 2013;14(1):329-32. [PubMed]
  • 45. Luevano-Gonzalez A, Guzman AQ, Ancer Rodriguez J, Ortiz Lopez R, Rojas Martinez A, Gonzalez Guerrero JF, et al. Analysis of DNA mismatch repair proteins expression and BRAF V600E mutation in a subset of early- and late-onset colorectal carcinoma patients in Mexico. Arch Med Res. 2011;42(6):457-62. [DOI] [PubMed]
  • 46. Bond CE, Umapathy A, Buttenshaw RL, Wockner L, Leggett BA, Whitehall VL. Chromosomal instability in BRAF mutant, microsatellite stable colorectal cancers. PLoS One. 2012;7(10):eee47483 [DOI] [PubMed]
  • 47. Samowitz WS, Sweeney C, Herrick J, Albertsen H, Levin TR, Murtaugh MA, et al. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res. 2005;65(14):6063-9. [DOI] [PubMed]
  • 48. Ghaffarpour M, Mohammadi Pargoo E, Sobhani S, Pirmoradi S, Mostakhdemin Hosseini Z, Kamali F. PIK3CA and BRAF mutational status and association with clinicopathological features in Iranian colonrectal cancer patients. Cancer Res. 2011;71:3799. [DOI]
  • 49. Javadi F, Geramizadeh B, Mirzai M. BRAF Gene Mutation Analysis in Colorectal Cancer in South of Iran. Ann Colorectal Res. 2014;2(2):eee19917
  • 50. Vatandoost N, Ghanbari J, Mojaver M, Avan A, Ghayour-Mobarhan M, Nedaeinia R, et al. Early detection of colorectal cancer: from conventional methods to novel biomarkers. J Cancer Res Clin Oncol. 2015. [DOI] [PubMed]
  • 51. Bidgoli SA, Azizi E, Zavarhei MD. Association between p53 expression and Bcl-2, P-glycoprotein, topoisomerase II alpha, thymidylate synthase and thymidine phosphorylase as potential therapeutic targets in colorectal cancer patients. Pak J Biol Sci. 2007;10(19):3350-5. [PubMed]
  • 52. Ghavam-Nasiri MR, Rezaei E, Ghafarzadegan K, Seilanian-Toosi M, Malekifard H. Expression of p53 in colorectal carcinoma: correlation with clinicopathologic features. Arch Iran Med. 2007;10(1):38-42. [PubMed]
  • 53. Doosti A, Zamani M, Ghasemi Dehkordi P, Taheri Sh , Banitalebi M, Mahmoudzadeh M. Association of the p53 codon 72 polymorphism with colorectal cancer in South West of Iran. Sci Res Essays. 2011;6(15):3148-52.
  • 54. Mojtahedi Z, Haghshenas MR, Hosseini SV, Fattahi MJ, Ghaderi A. p 53 codon 72 polymorphism in stomach and colorectal adenocarcinomas in Iranian patients. Indian J Cancer. 2010;47(1):31-4. [DOI] [PubMed]
  • 55. Dastjerdi MN. TP53 codon 72 polymorphism and P53 protein expression in colorectal cancer specimens in Isfahan. Acta Med Iran. 2011;49(2):71-7. [PubMed]
  • 56. Golmohammadi R, Namazi MJ, Nikbakht M, Salehi M, Derakhshan MH. Characterization and Prognostic Value of Mutations in Exons 5 and 6 of the p53 Gene in Patients with Colorectal Cancers in Central Iran. Gut Liver. 2013;7(3):295-302. [DOI] [PubMed]
  • 57. Nejad AL, Yaghoobi MM. Mutation Analysis of TP53 Tumor Suppressor Gene in Colorectal Cancer in Patients from Iran (Kerman Province). Iran J Basic Med Sci. 2012;15(1):683-90. [PubMed]
  • 58. Hasanpour M, Galehdari H, Masjedizadeh A, Ajami N. A unique profile of adenomatous polyposis coli gene mutations in Iranian patients suffering sporadic colorectal cancer. Cell J. 2014;16(1):17-24. [PubMed]
  • 59. Kashfi SM, Golmohammadi M, Behboudi F, Nazemalhosseini-Mojarad E, Zali MR. MUTYH the base excision repair gene family member associated with colorectal cancer polyposis. Gastroenterol Hepatol Bed Bench. 2013;6(Suppl 1):S1-S10. [PubMed]
  • 60. Akbari Z, Safari-Alighiarloo N, Haghighi MM, Vahedi M, Mirtalebi H, Azimzadeh P, et al. Lack of influence of the SMAD7 gene rs2337107 polymorphism on risk of colorectal cancer in an Iranian population. Asian Pac J Cancer Prev. 2014;15(11):4437-41. [PubMed]
  • 61. Farzanehfar M, Vossoughinia H, Jabini R, Tavassoli A, Saadatnia H, Khorashad AK, et al. Evaluation of methylation of MGMT (O(6)-methylguanine-DNA methyltransferase) gene promoter in sporadic colorectal cancer. DNA Cell Biol. 2013;32(7):371-7. [DOI] [PubMed]
  • 62. Mojtahedi Z, Erfani N, Haghshenas MR, Hosseini SV, Ghaderi A. Association of FoxP3/Scurfin Germline Polymorphism (C-2383T/rs3761549) with Colorectal Cancer. Ann Colorectal Res. 2013;1(1):12-6.
  • 63. Mojtahedi Z, Mohmedi M, Rahimifar S, Erfani N, Hosseini SV, Ghaderi A. Programmed death-1 gene polymorphism (PD-1.5 C/T) is associated with colon cancer. Gene. 2012;508(2):229-32. [DOI] [PubMed]

Table 1.

Reported MMR Gene Mutations from Different Studies on Iranian Population

Author Year Study Population Number of Cases Methology MSI a MSI-H a MSI-L a MSS a Most Common Instable Marker
Bishehsari et al. ( 16 ) 2006 HNPCC 12 PCR-Sequencing 100 100 None 0 -
Sporadic 170 19.40 19.40 80.60
Salehi et al. ( 17 ) 2008 HNPCC 32 PCR-SSCP-Sequencing 62.50 - - 37.50 -
Haghighi et al. ( 19 ) 2010 HNPCC 78 PCR-sequencing 41 26.90 14.10 59 NR- 21
Moghbeli et al. ( 20 ) 2011 Sporadic CRC 67 PCR-sequencing 43.30 26.90 16.40 56.70 BAT-25
Shemirani et al. ( 9 ) 2011 HNPCC 80 PCR -sequencing - - - - NR-21
Sporadic CRC 80 - - - -
Faghihi et al. ( 21 ) 2012 Sporadic 96 PCR-sequencing 22.90 - - 77.10 BAT-26
Brim et al. ( 22 ) 2014 Sporadic 27 PCR-Sequencing 66.60 14.80 18.50 44.40 -
Zeinalian et al. ( 24 , 25 ) 2015 HNPCC 31 IHC and PCR-sequencing 29 19.40 9.60 61 BAT-26
a Data are presented as %.

Table 2.

Reported KRAS Mutation in Previous Studies on Iranian Population

Study Year Number of Cases Methodology Prevalence of KRAS Mutation
Shemirani ( 29 ) a 2011 48 PCR-Sequencing 12.5%
Naghibalhossaini ( 30 ) 2011 86 PCR-RFLP 28%
Bishehsari ( 16 ) a 2006 182 PCR-Sequencing 37.4%
Sobhani ( 31 ) a 2010 59 PCR-Sequencing 20.3%
Omidifar ( 32 ) a 2015 100 PCR-Sequencing 32%
a Most common mutation 12 G - A.

Table 3.

Reported BRAF Mutation in the Previous Studies in Iranian Population

Study Year No of CASES Methodology Percentage
Brim ( 18 ) 2008 53 PCR-Sequencing 2%
Naghibalhossaini ( 30 ) 2011 110 PCR-RFLP 0
Ghaffarpour ( 48 ) 2011 27 PCR-Sequencing 3.7%
Javadi ( 49 ) 2014 100 PCR-Sequencing 0