KRAS and BRAF Hotspot Variants Show Lower Prevalence in Bangladeshi Colorectal Cancer Patients

Document Type : Research Articles

Authors

1 Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka, Bangladesh.

2 Department of Biotechnology and Genetic Engineering, United International University, Dhaka, Bangladesh.

3 Bangladesh Medical University (BMU), Dhaka, Bangladesh.

4 National Institute of Cancer Research and Hospital (NICRH), Dhaka, Bangladesh.

Abstract

Objective: Colorectal cancer (CRC) is the second-leading cause of cancer-related mortality globally, with a rising incidence in Bangladesh. This study aims to identify pathogenic KRAS and BRAF mutations contributing to anti-EGFR resistance in CRC patients. Methods: Two sets of primers were used: one was adopted from a published paper, and another was designed using Primer3Plus. They were optimized for specific PCR amplicons of 173 bp and 230 bp from exon 2 of KRAS and exon 15 of BRAF, respectively. Targeted Sanger sequencing was performed to analyze mutations in these amplicons in 46 CRC patient samples. Results: KRAS mutations were detected in 5 samples (10.87%), comprising two G12D, one G12V, and two G13D variants. Notably, no BRAF V600E mutation was identified. These results stand in sharp contrast to global data, where KRAS mutations at these loci occur in approximately 40% of cases and BRAF V600E mutations in about 10%. Such mutations are clinically significant because they confer resistance to anti-EGFR therapy, underscoring the distinct molecular profile observed in this cohort. Conclusion: The lower prevalence of KRAS and BRAF mutations indicates the potential effectiveness of anti-EGFR therapies in Bangladeshi CRC patients than other populations.

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