Relationship between Common KRAS Gene Mutations and Clinicopathological Features of Patients with Colorectal Cancer in Isfahan, Iran

Abstract

Background:

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide. KRAS mutations are found in 20-30% of the cases and are associated with poor response to anti-EGFR therapies. Mutations in the KRAS gene induce the constitutive protein activity by eliminating the GTPase activity in the signal transduction pathway. Somatic mutations of KRAS are located up to 90% in codons 12 and 13 of exon 2. Therefore, this study evaluated the association between KRAS mutations and clinicopathological features of patients with CRC in Isfahan.

Materials and Methods:

This study was performed on 52 patients with CRC referred to Al-Zahra Hospital in Isfahan. Total DNA was extracted from fresh tumor and normal tissues. The exon 2 of KRAS gene was amplified and sequenced for detection of the point mutations. After mutation analysis, the clinical and pathological associations of mutant genes were assessed.

Results:

The prevalence of KRAS gene mutation was 15/4% (8 out of the 52 cases). Six mutations found in codon 12 (75%), were G12D and G12A, and two mutations found in codon 13 (25%) were G13D. Common tumor sites were rectum and rectosigmoid. The mean age of the patients was 61/2±13/9 years (range: 31-87 years). There was no significant relationship between the mutations and clinicopathological features of patients with CRC (p>0.05).

Conclusions:

This paper presents new results on the frequency of KRAS mutations in patients with CRC. KRAS mutations could be used as molecular biomarkers to predict the lack of response to anti-EGFR monoclonal antibodies.