<i>KRAS</i> and <i>BRAF</i> Mutation Rates and Survival Outcomes in Colorectal Cancer in an Ethnically Diverse Patient Cohort
<i>KRAS</i> and <i>BRAF</i> 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 environmenta...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/24/17509 |
| Summary: | <i>KRAS</i> and <i>BRAF</i> 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 <i>KRAS</i>/<i>BRAF</i> 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 <i>KRAS</i>/<i>BRAF</i> 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). <i>KRAS</i>/<i>BRAF</i> 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 <i>KRAS</i> mutation rates between Caucasians (41.1%), Middle Easterners (47.9%), Asians (44.8%), and South Americans (25%) (<i>p</i> = 0.34). <i>BRAF</i> mutation rates differed significantly between races (<i>p</i> = 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 <i>KRAS</i> mutation rate (<i>p</i> = 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 <i>KRAS</i> mutation rates across races raises the possibility that the differences in <i>KRAS</i> 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 <i>BRAF</i> mutation rates differ significantly between races, suggesting racial genetic differences may be responsible for the discrepant <i>BRAF</i> mutation rates reported from different countries. |
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| ISSN: | 1661-6596 1422-0067 |