KRAS and BRAF Mutation Rates and Survival Outcomes in Colorectal Cancer in an Ethnically Diverse Patient Cohort

Paul Habashy; Vivienne Lea; Kate Wilkinson; Bin Wang; Xiao-Juan Wu; Tara Laurine Roberts; Weng Ng; Tristan Rutland; Joseph William Po; Therese Becker; Joseph Descallar; Mark Lee; Scott Mackenzie; Ruta Gupta; Wendy Cooper; Stephanie Lim; Wei Chua; Cheok Soon Lee

doi:10.3390/ijms242417509

KRAS and BRAF Mutation Rates and Survival Outcomes in Colorectal Cancer in an Ethnically Diverse Patient Cohort

Int J Mol Sci. 2023 Dec 15;24(24):17509. doi: 10.3390/ijms242417509.

Authors

Paul Habashy^{1

2}, Vivienne Lea^{1

3}, Kate Wilkinson⁴, Bin Wang^{1

5}, Xiao-Juan Wu³, Tara Laurine Roberts^{2

5

6}, Weng Ng^{2

4

5

6}, Tristan Rutland^{1

2

3}, Joseph William Po^{5

7}, Therese Becker^{2

5

6}, Joseph Descallar^{5

6}, Mark Lee⁸, Scott Mackenzie^{2

9}, Ruta Gupta¹⁰, Wendy Cooper^{1

10

11}, Stephanie Lim^{2

5

12}, Wei Chua^{2

4

5}, Cheok Soon Lee^{1

2

3

5

6

10}

Affiliations

¹ Discipline of Pathology, School of Medicine, Western Sydney University, Sydney, NSW 2560, Australia.
² Liverpool Clinical School, Western Sydney University, Sydney, NSW 2170, Australia.
³ Department of Anatomical Pathology, Liverpool Hospital, Sydney, NSW 2170, Australia.
⁴ Department of Medical Oncology, Liverpool Hospital, Sydney, NSW 2170, Australia.
⁵ Ingham Institute for Applied Medical Research, Liverpool Hospital, Sydney, NSW 2170, Australia.
⁶ South Western Sydney Clinical School, University of New South Wales, Sydney, NSW 2170, Australia.
⁷ Surgical Innovations Unit, Department of Surgery, Westmead Hospital, Sydney, NSW 2140, Australia.
⁸ Department of Radiation Oncology, Liverpool Hospital, Sydney, NSW 2170, Australia.
⁹ Department of Surgery, Liverpool Hospital, Sydney, NSW 2170, Australia.
¹⁰ Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
¹¹ Sydney Medical School, University of Sydney, Sydney, NSW 2050, Australia.
¹² Department of Medical Oncology, Campbelltown Hospital, Sydney, NSW 2560, Australia.

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.

Keywords: BRAF; KRAS; MMR; colorectal cancer; ethnically diverse; genetic screening; racial–ethnic.

MeSH terms

Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / pathology
Humans
Mutation
Mutation Rate
Proto-Oncogene Proteins B-raf* / genetics
Proto-Oncogene Proteins p21(ras)* / genetics
Retrospective Studies

Substances

BRAF protein, human
KRAS protein, human
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins p21(ras)

Grants and funding

This research received no external funding.