The Mutation Rates of NRAS, KRAS, BRAF and PIK3CA and Their Associations with Clinicopathological Features in Ugandan Colorectal Cancer Patients | Chapter 6 | Medical Science: Recent Advances and Applications Vol. 10

 

Introduction: In the clinical assessment of progression and development of colorectal cancer (CRC), mutations in KRAS, BRAF, PIK3CA, and NRAS genes are critical factors. In Uganda, however, the data regarding the genetic profile of CRC patients is limited except for BRAF and KRAS mutations. The objective of this study was to determine the mutational spectrum of these genes and the association between the clinicopathological features and these mutations in Ugandan CRC patients.

 

Methodology: To reach these objectives, a total of 127 patients with CRC were recruited between 2008-2021. Mutations in BRAF, KRAS, PIK3CA and NRAS were determined using pyrosequencing and PCR.

 

Results: BRAF, KRAS, PIK3CA, and NRAS mutations were identified in 3.2%, 6.3%, 29.1% and 2.4% of the cases, respectively. There were some significant correlations between BRAF and PIK3CA mutations and clinicopathological features. Mutations in BRAF were shown to be associated with the SRCC histopathological subtype 4(50%) (p=0.011) and were predominantly found in right-sided colon tumours 3(75%) (p=0.023). Whilst PIK3CA mutations were more prevalent in females 23, 62.2%) (p=0.012). There was a tendency for PIK3CA mutations to be associated with increasing size of the tumour; T3: 21(56.8%) compared to T1: 3(8.1%) (p=0.032).

 

Conclusions: This is the first study in Uganda analysing all four genes simultaneously. Our study revealed a high PIK3CA mutation rate similar to other studies in the Western world. The BRAF mutation was predominantly found in right-sided colon tumours and associated with poor prognostic markers such as small cell colorectal carcinoma. The PIK3CA mutation was associated with larger tumours in Ugandan CRC patients. KRAS mutations may be a poor prognostic factor in Ugandan CRC patients, and KRAS wild-type CRC patients could benefit from EGFR-targeted drugs. The detection of NRAS, KRAS, BRAF and PIK3CA gene mutations and their associated clinicopathological features may influence targeted therapy or cancer management strategies in Sub-Saharan Africa.

 

 

Author(s) Details

Wismayer Richard
Department of Surgery, Masaka Regional Referral Hospital, Masaka, Uganda, Department of Surgery, Faculty of Health Sciences, Equator University of Science and Technology, Masaka, Uganda, Department of Surgery, Faculty of Health Sciences, Habib Medical School, IUIU University, Kampala, Uganda, Department of Pathology, School of Biomedical Sciences, College of Health Sciences, MakerereUniversity, Kampala, Uganda and Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.

 

Matthews Rosie
Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.

 

Whalley Celina
Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

 

Kiwanuka Julius
Department of Epidemiology and Biostatistics, College of Health Sciences, Makerere University, Kampala, Uganda.

 

Kakembo Fredrick Elishama
Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda and African Centre of Excellence in Bioinformatics and Data Intensive Sciences, Infectious Diseases Institute, Makerere University, Kampala, Uganda.

 

Thorn Steve
Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK and Department of Oncology, University of Oxford, Oxford, UK.

 

Wabinga Henry
Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.

 

Odida Michael
Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda and Department of Pathology, Faculty of Medicine, Gulu University, Gulu, Uganda.

 

Tomlinson Ian
Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK and Department of Oncology, University of Oxford, Oxford, UK.

 

Please see the book here:- https://doi.org/10.9734/bpi/msraa/v10/6179