Mutation spectra of RAS gene family in colorectal cancer

Abstract

Background: The clinicopathologic features and frequency of KRAS mutations in colorectal cancer (CRC) patients have been reported; however, the characteristics and impact of NRAS and HRAS mutations on the survival of CRC patients have seldom been addressed.

Methods: Under institutional review board approval, 1,519 CRC patients who underwent surgery were enrolled. Mutation status of RAS was determined by polymerase chain reaction and mass spectrophotometry.

Results: The frequency of KRAS, NRAS, and HRAS mutations was 39.6%, 4.3%, and 1.7%, respectively. The KRAS mutation was associated with fewer left-sided tumors, fewer poor differentiated tumors, more mucin component, and less lymphovascular invasion. The NRAS or HRAS mutations were not associated with any of the clinicopathologic features examined. After univariate analysis, only NRAS mutation was associated with patients' overall and disease-free survival. However, the association of NRAS with patients' overall and disease-free survival disappeared after stepwise elimination.

Conclusions: This study demonstrates the clinicopathologic characteristics of CRC patients with RAS mutations. Patients with NRAS mutation tended to have worse outcomes.

Keywords: Colorectal cancer; HRAS; KRAS; NRAS; Survival.