KRAS, NRAS, and BRAF Mutation Pattern in Metastatic Colorectal Cancer: A Study from Northwest Iran

Abstract

Introduction: Colorectal cancer is currently the third most common cancer in terms of incidence and mortality in Iran. Different gene mutations may confer different degrees of biological aggressiveness and reduce the effectiveness of targeted therapeutic strategies in metastatic Colorectal Cancer (mCRC) patients. Aim: To evaluate any mutation pattern in mCRC, and then evaluate clinical and epidemiological correlations with the detected mutations. Materials and Methods: This study was a cross-sectional analytical study, and all mCRC cases referred to two main central hospitals and oncologists’ clinics, in Tabriz, Iran, from January 2016 to November 2018 were enrolled. KRAS, NRAS, and BRAF mutation tests were performed routinely for all mCRC cases before considering any treatment strategies. Idylla Biocartis NV system{Test Type Package (TTP)}, determined the presence of mentioned mutations. Logistic regression models were used to statistically analysis. Results: The present authors included 173 cases with confirmed mCRC. Among 102 patients with KRAS gene mutation detection, the frequency of mutations was 38.23% (n=39) while most were in exon 2, codon 12 (61.54%), followed by patients who had mutations in codon 13 (n=5, 12.82%). NRAS mutations were only observed in one patient (1.33%) from among the 75 cases who were tested. BRAF codon 600 was tested in 39 cases, and only one case (2.56%) had the mutation. Patients with leftsided tumours had about 9.5 times higher likelihood of KRAS mutation than right-sided tumours (OR=9.64; 95% CI=1.24- 75.27). Smoking increased the odds of KRAS mutation about 50%, and mCRC who had alcohol consumption had about two times more likelihood of mutation. Conclusion: The overall frequency of KRAS mutations in the present study was high, while the frequency of KRAS mutations in mCRC patients is lower in Asian populations. KRAS mutation results in this study were most similar to European populations.

Keywords

• colorectal neoplasm
• metastasis
• oncogene