BRAF Gene Mutation Analysis in Colorectal Cancer in South of Iran

Javadi, Farshid; Geramizadeh, Bita; Mirzai, Mitra

doi:10.17795/acr-19917

Cited by 10 publications

(7 citation statements)

References 42 publications

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“…A study by Brim et al showed that the frequency of this mutation was very low in Eastern countries 38. Results in Iran have been consistent with this study, and showed that BRAF mutations were present in 0%–3.7% of patients with CRC 17,36…”

Section: Discussionsupporting

confidence: 88%

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Association between proto-oncogene mutations and clinicopathologic characteristics and overall survival in colorectal cancer in East Azerbaijan, Iran

Dolatkhah

Somi

Kermani

et al. 2016

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BackgroundColorectal cancer (CRC) is the third-most common cancer in Iran. The increasing incidence of CRC in the past three decades has made it a major public health burden in the country. This study aimed to determine any relationship of specific mutations in CRCs with clinicopathologic aspects and outcome of patients.Materials and methodsThis study was conducted on 100 CRC patients by the case-only method. Polymerase chain-reaction products were analyzed by Sanger sequencing, and sequence results were compared with the significant KRAS and BRAF gene mutations in the My Cancer Genome database. Logistic regression models were used to detect associations of clinicopathologic characteristics with each of the mutations. Kaplan–Meier and Cox regression models were constructed to estimate overall survival in patients.ResultsA total of 26 subjects (26%) had heterozygote-mutant KRAS, and mutations were not detected in the amplified exon of BRAF in both tumor and normal tissues of the 100 CRCs. Rectal tumors had 1.53-fold higher likelihood of KRAS mutations than colon tumors, and men had 1.37-fold higher odds than women. The presence of metastasis increased the likelihood of KRAS mutations 2.36-fold over those with nonmetastatic CRCs. Compared to patients with KRAS wild-type cancers, those with KRAS mutations had significantly higher mortality (hazard ratio 3.74, 95% confidence interval 1.44–9.68; log-rank P=0.003).ConclusionBetter understanding of the causality of CRC can be established by combining epidemiology and research on molecular mechanisms of the disease.

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Section: Discussionsupporting

confidence: 88%

“…Controversial data are available on the prevalence of this mutation in different countries. The highest frequency is reported in the US and Australia, with 9.5%–12.5% of patients with CRC showing this mutation 36. Furthermore, 4.2%–4.4% of patients carry mutant genes 37.…”

Section: Discussionmentioning

confidence: 99%

Association between proto-oncogene mutations and clinicopathologic characteristics and overall survival in colorectal cancer in East Azerbaijan, Iran

Dolatkhah

Somi

Kermani

et al. 2016

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“…Frequency of BRAF gene mutation in the primary tumour samples was reported in 64 studies carried out among 19,484 samples. The frequencies varied from zero in the studies carried out by Dolatkhah et al, (2015), Javadi, Geramizadeh, and Mirzai (2014) and Naghibalhossaini, Hosseini, Mokarram, and Zamani, (2011) in Iran, Raskin, Dakubo, Palaski, Greenson, and Gruber, (2013) in the USA and Ozen et al, (2013) in Turkey to 42.5% in the study conducted by Phipps et al, (2013) in New Zealand; Table 2). Results of the heterogeneity tests showed significant heterogeneity between the primary frequencies (I-squared: 97.2%, Q: 2,220.8, p < .001).…”

Section: Idmentioning

confidence: 98%

Prevalence of BRAF gene mutation in samples of primary and metastatic colorectal cancer: A meta‐analysis

et al. 2019

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Introduction Understanding the prevalence and biology of BRAF gene can improve the treatment methods of cancerous patients. This study aims to estimate the prevalence of BRAF gene mutation in samples of primary and metastatic colorectal cancer using meta‐analysis method. Methods We searched PubMed, Scopus, ScienceDirect, Ovid and Google Scholar motor engine using MeSH terms of relevant keywords. During the screening phase, titles, abstracts and full texts were reviewed and risk of bias was assessed for all selected papers based on Newcastle–Ottawa Scale (NOS) checklist. The results of the primary studies were combined using meta‐analysis. Results Of 95 eligible studies entered into the meta‐analysis, prevalence of BRAF gene mutation had been assessed among 19,484 primary tumour samples as well as 12,256 metastatic samples. The total prevalence of BRAF gene mutation among primary tumour samples was estimated as of 10.16% (8.09–12.22) in the world, 0.41% (0–1.89) in EMRO region, 10.06% (7.54–12.59) in EURO region, 10.33% (7.24–13.43) in SEARO region and 11.33% (7.29–15.37) in WPRO region. The pooled estimates for BRAF gene mutation in metastatic samples were 6.53% (5.09–7.96), 8.07% (5.57–10.56), 5.38% (3.75–7.02) and 5.55% (1.72–9.38) for all regions, EURO, WPRO and PAHO regions respectively. Conclusion Our results showed evidences of BRAF gene mutation in one‐tenth of primary colorectal tumour samples in EURO, PAHO, SEARO and WPRO regions which was considerably higher than that of the EMRO region.

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“… 3 , 4 Activating mutations in the RAS genes occur in approximately 20% of all human cancers, mainly in codons 12, 13, or 61. 5 - 7 Among the RAS family, mutations in KRAS account for about 85% of all RAS mutations in human tumors; NRAS for about 15%; and HRAS for less than 1%. 6 RAS mutations are useful markers for predicting responses to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (like cetuximab or panitumumab), especially in metastatic colorectal cancers (CRC).…”

Section: Introductionmentioning

confidence: 99%

Frequency of NRAS Gene Mutation in Wild Type KRAS and BRAF Colorectal Cancers; a Single Center Study

Momenzadeh

Mirzai

Jowkar

et al. 2018

Middle East J Dig Dis

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BACKGROUND Incidence of colorectal cancer is increasing in countries such as Iran. Molecular biomarkers play very important role in the diagnosis, treatment, and prognosis of this cancer. Mutation in the RAS family (including KRAS and NRAS) is one of these important molecular biomarkers, which should be tested before starting treatment with anti-EGRF (Epidermal growth factor) drugs. Objectives: There has been very few reports about the frequency of NRAS mutation from Iran and no study from south of the country. In this article we will describe our experience about the frequency of NRAS mutation in colorectal cancers from the largest referral center in the south of Iran. METHODS During 5 years (2011-2015), we had 52 cases of colorectal cancers with wild type KRAS and BRAF in the hospitals affiliated to Shiraz University of Medical Sciences with enough tissue for molecular studies. NRAS mutation analysis was performed on paraffin embedded formalin fixed tissue of these cases by polymerase chain reaction (PCR)-sequencing method. RESULTS Among these 52 cases of colorectal cancer with wild type KRAS and BRAF, there has been 3 (5.7%) cases with mutant NRAS. One of the mutations has been in codon 12 and two in codon 61. No mutation in codon 13 was found. All the three cases were women with stage IV and well differentiated histomorphology. CONCLUSION Our results showed that frequency of NRAS mutation in colorectal cancer is rare, which is very close to other studies from different geographic areas of the world.

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BRAF Gene Mutation Analysis in Colorectal Cancer in South of Iran

Cited by 10 publications

References 42 publications

Association between proto-oncogene mutations and clinicopathologic characteristics and overall survival in colorectal cancer in East Azerbaijan, Iran

Association between proto-oncogene mutations and clinicopathologic characteristics and overall survival in colorectal cancer in East Azerbaijan, Iran

Prevalence of BRAF gene mutation in samples of primary and metastatic colorectal cancer: A meta‐analysis

Frequency of NRAS Gene Mutation in Wild Type KRAS and BRAF Colorectal Cancers; a Single Center Study

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