Abstract

Background and objective: Colorectal cancer (CRC) is the second most fatal and the third most common malignant tumor in the world. Mutation in NRAS and KRAS genotypes has been reported in this type of cancer. The present study was conducted to examine the prevalence of these two genotypes in CRC and their association with clinical outcomes of patients with advanced CRC.

Materials and methods: The present study was a prospective one conducted on 81 stage IV metastatic colorectal cancer patients who were cured with and without chemotherapy at Hiwa Cancer Hospital in Sulaimani, Iraq from January 2016 to December 2019. KRAS and NRAS mutations were tested in the patients on formalin-fixed paraffin-embedded tissue. The collected data were analyzed through Statistical Package for Social Sciences (version 23.0).

Results: The patients’ mean age was 53.5 years. CRC was more prevalent among males. KRAS mutant alone, and KRAS and NRAS mutants were respectively seen in 30.9% and 6.1% of the patients. Prevalence of stage IV CRC was 30.5%, and RAS genotype prevalence was 37%. KRAS and NRAS status had no significant association with the patients’ characteristics like sex, age, primary site, tumor grade, or smoking (p-value>0.05). Although females had a better 1-year survival outcome, it did not have a significant association with sex (p-value=0.49). One-year survival was significantly better in patients with chemotherapy with treatment (p-value=0.01) and grade I CRC (p-value=0.05). Overall survival was not significantly different between males and females, different ages, or different tumor sites (p-value>0.05), while it was significantly better in grade I CRC patients (p-value=0.04) and those who had chemotherapy with treatment (p-value=0.01). One-year survival and overall survival were not significantly different between patients undergone chemotherapy with Cetuximab and Bevacizumab (p-value>0.05).

Conclusion: The prevalence of KRAS mutant alone, and KRAS and NRAS mutants were respectively 30.9% and 6.1%. Factors like sex, age, tumor initial site, tumor grade, and smoking have no significant association with KRAS and NRAS genotype status. Females had better survival outcomes than males. Determination of KRAS and NRAS genotype in metastatic CRC is required for choosing the most appropriate therapy.

Keywords: colorectal cancer (CRC), KRAS genotype, NRAS genotype, clinical outcomes, survival