KRAS and BRAF mutation rates and survival outcomes in colorectal cancer in an ethnically diverse patient cohort

P. Habashy, Vivienne Lea, K. Wilkinson, B. Wang, X. -J. Wu, Tara Laurine Roberts, W. Ng, Tristan Rutland, J. W. Po, Therese Becker, J. Descallar, M. Lee, Scott Mackenzie, R. Gupta, Wendy Cooper, Stephanie Lim, Wei Chua, Cheok Soon Lee

Research output: Contribution to journalArticlepeer-review

Abstract

KRAS and BRAF mutation rates in colorectal cancer (CRC) reported from various mono-ethnic studies vary amongst different ethnic groups. However, these differences in mutation rates may not be statistically significant or may be due to differences in environmental and/or laboratory factors across countries rather than racial genetic differences. Here, we compare the KRAS/BRAF mutation rates and survival outcomes in CRC between ethnic groups at a single institution. We also investigate the contributions of genetic, environmental, and laboratory factors to the variations in KRAS/BRAF mutation rates reported from different countries. Clinicopathological data from 453 ethnically diverse patients with CRC were retrospectively analyzed at Liverpool Hospital, NSW Australia (2014–2016). KRAS/BRAF mutations were detected using real-time PCR (Therascreen kits from Qiagen). Mismatch repair (MMR) status was determined using immunohistochemical staining. Four ethnic groups were analyzed: Caucasian, Middle Eastern, Asian, and South American. Overall survival data were available for 406 patients. There was no significant difference in KRAS mutation rates between Caucasians (41.1%), Middle Easterners (47.9%), Asians (44.8%), and South Americans (25%) (p = 0.34). BRAF mutation rates differed significantly between races (p = 0.025), with Caucasians having the highest rates (13.5%) and Middle Easterners the lowest (0%). A secondary analysis in which Caucasians were divided into three subgroups showed that ethnic grouping correlated significantly with KRAS mutation rate (p = 0.009), with central and eastern Europeans having the highest rates (58.3%). There were no significant differences in overall survival (OS) or disease-free survival (DFS) between the four races. The similarity in KRAS mutation rates across races raises the possibility that the differences in KRAS mutation rates reported from various countries may either not be statistically significant or may be due to environmental and/or laboratory factors rather than underlying racial genetic differences. In contrast, we verified that BRAF mutation rates differ significantly between races, suggesting racial genetic differences may be responsible for the discrepant BRAF mutation rates reported from different countries.
Original languageEnglish
Article number17509
Number of pages20
JournalInternational Journal of Molecular Sciences
Volume24
Issue number24
DOIs
Publication statusPublished - Dec 2023

Open Access - Access Right Statement

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Fingerprint

Dive into the research topics of 'KRAS and BRAF mutation rates and survival outcomes in colorectal cancer in an ethnically diverse patient cohort'. Together they form a unique fingerprint.

Cite this