Mutation Status and Prognostic Value of KRAS and BRAF in Southeast Iranian Colorectal Cancer Patients: First Report from Southeast of Iran.

Abstract

This study aimed to determine any association of KRAS and BRAF mutations in colorectal cancer with clinicopathological features and overall survival (OS) of Southeast Iranian colorectal cancer (CRC) patients. Overall, KRAS and BRAF status were assessed in 100 Iranian CRC subjects. A hundred consecutive stages I-IV CRC patients, who underwent surgical tumor resection from February 2012 to August 2015, were prospectively attained from three centers and were enrolled in the research. Direct sequencing and real-time PCR methods were used to the detection of KRAS and BRAF mutations, respectively. Logistic regression models were used to detect associations of KRAS and BRAF mutations with clinical/clinicopathological features. Kaplan-Meier model was used to estimate overall survival. In total, KRAS and BRAF mutations were detected in 29 (29%) and 7 (7%) of 100 CRC patients, respectively. BRAF mutations that all comprised V600E and KRAS mutations were found in codon 12, 13, and 61 (72.4%, 20.7 and 6.9%), respectively. In a multivariate analysis, older age (≥ 60) was significantly associated with higher KRAS mutations rate and high BRAF mutation rate was significantly associated with older age (≥ 60) and poorly differentiated tumors. KRAS and BRAF mutant vs. wild type of KRAS and BRAF, 5-year OS was 62.1% vs. 71.8% (p value > 0.05) and 57.1% vs. 67.7% (p value > 0.05), respectively. Mutations were found in both KRAS and BRAF genes in Iranian colorectal cancers patients and were associated with clinical/clinicopathologic features. Our data emphasizes the importance of these molecular features in Iranian CRC patients.