Is the disease profile in metastatic colorectal cancer still driven by the mutational parameters as before? A tertiary care center study from India in 2020

Abstract

Background: The pathophysiology of colorectal cancer (CRC) is believed to be driven primarily by anomalies in the molecular pathway mechanisms. Mutations in KRAS, NRAS, and BRAF genes are closely associated with tumor differentiation, invasion, and metastasis. These are now recognized as important targets for clinical treatment of metastatic CRC to determine the response to therapy and final prognosis of the disease. The study investigates the relationship of KRAS, NRAS, and BRAF gene mutations in the Indian population in the current era. Materials and Methods: A total of 120 patients including 50 patients having metastatic disease, all with proven histological diagnosis of CRC were included. They were followed up for examination of clinical signs and performance status. Ethical approval was obtained from the Ethical Committee at Army Hospital (R and R), New Delhi (IRB No. 91/2016). Results: This prospective study shows that the young adults (<45 years) presented with an aggressive biology of disease with advanced disease at presentation and have higher mortality rates due to poor response to therapy. NRAS and BRAF mutations were found mainly with left and right sides, respectively. The right-side CRC had poor prognosis and responses to therapies (P = 0.07 and P = 0.005, respectively). NRAS and BRAF mutations were found mostly in women having comorbidities. Young individuals with a positive family history of CRC must be investigated early for tumor markers for better treatment outcomes. Conclusion: This planned investigation affirmed that the Indian populace had more right-side CRC which was metastatic predominantly. RAS and BRAF changes were related essentially with left- and right-side CRCs, respectively. However, both had a poor prognosis and reactions to treatments. NRAS mutation might be a significant marker as it is observed solely in young females with left-side CRC and had a poor prognosis due to an aggressive tumor. BRAF transformations are higher in the Indian populace in contrast to the western information.