A study of BRAF mutation in colorectal carcinoma in Indian population

Saxena, Shivam; Srinivas, V.; Deb, Prabal; Raman, Deep Kumar; Jagani, Rajat

doi:10.4103/jcrt.jcrt_26_17

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…Previous studies on the prevalence of BRAF mutations in CRC from the West have revealed a mutation frequency of 5 to 20%, 1 2 while studies from the Asian continent have reported a slightly lower frequency of 4 to 14%. 3 4 5 6 A very low frequency of BRAF alteration was observed in this cohort that could indicate alternate key driver mutations responsible for disease progression. The median OS in patients harboring BRAF V600E was found to be ∼19.2 months ( p = 0.488) in this series.…”

Section: Discussionmentioning

confidence: 80%

The Prevalence of BRAF, PIK3CA, and RAS Mutations in Indian Patients with Colorectal Cancer

Shetty

Vengurlekar

Kapoor

et al. 2022

South Asian J Cancer

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Introduction The present study evaluates the mutation pattern and frequency of BRAF, PIK3CA and RAS in colorectal carcinoma observed in the tertiary cancer center in India. Materials and Methods Consecutive cases of colorectal adenocarcinoma (n = 330) registered from January 2015 to December 2019 (5-year duration) were selected for the study. Molecular analysis for BRAF.PIK3CA (exon 9 and 20) and RAS (KRAS&NRAS) was performed on representative formalin-fixed paraffin-embedded tissues by Sanger sequencing. Results were correlated with clinicopathological features. Patient overall survival (OS) was obtained using Kaplan–Meier method. Results The study cohort was in the age range of 22 to 81 years (median age: 52 years) that included 202 males and 96 females (male: female ratio 2.1:1). BRAF V600E mutation was observed in three cases (1%), while 17 cases (5.7%) had mutations in the PIK3CA gene (exon 9 or exon 20). Mutation analysis for RAS gene (KRAS&NRAS) was observed among 42 (15.4%) cases with KRAS mutation and 11 (4%) cases were positive for NRAS mutations. Among RAS, KRAS G12D was the predominant mutation. Median OS with wild-type RAS was 46.6 months (95% confidence interval [CI]: 22.4–70.8), while for RAS mutated patients, it was 25.6 months (95% CI: 16.7–34.5), hazard ratio: 1.7 (95% CI: 1.1–2.7, p = 0.025). Conclusion This study evaluated the prevalence of BRAF, PIK3CA and RAS mutations in the Indian cohort and its impact on clinical behavior. There was lower incidence of BRAF mutations in this cohort and PIK3CA mutation (single) did not impact survival of the patients.

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Section: Discussionmentioning

confidence: 80%

The Prevalence of BRAF, PIK3CA, and RAS Mutations in Indian Patients with Colorectal Cancer

Shetty

Vengurlekar

Kapoor

et al. 2022

South Asian J Cancer

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“…Higher KRAS mutation rates have been reported among African Americans compared to Caucasians [35], while a review showed that Hispanics had a higher rate of KRAS mutations than Caucasians (though this was not statistically significant) [11]. The BRAF mutation rates reported in Asian studies tend to be lower than those reported in Western studies [11,12,14,17,19,20,[36][37][38][39][40][41][42]. However, it is difficult to determine whether these differences in KRAS and BRAF mutation rates reported from independent studies represent true racial differences, because no statistical tests were performed to compare the studies' cohorts and the mutation detection methods may have varied between studies.…”

Section: Introductionmentioning

confidence: 99%

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

Habashy,

Lea,

Wilkinson

et al. 2023

IJMS

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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.

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A Systematic Review and Meta-analysis on the Occurrence of Biomarker Mutation in Colorectal Cancer among the Asian Population

Afolabi

Salleh

Zunita

et al. 2022

BioMed Research International

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Globally, colorectal carcinoma (CRC) is the third most common cancer and the third major cause of cancer-related death in both sexes. KRAS and BRAF mutations are almost mutually exclusively involved in the pathogenesis of CRC. Both are major culprits in treatment failure and poor prognosis for CRC. Method. A systematic review and meta-analysis of various research was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. This trial is registered with PROSPERO CRD42021256452. The initial search included 646 articles; after the removal of noneligible studies, a total of 88 studies was finally selected. Data analysis was carried out using OpenMeta Analyst and Comprehensive Meta-Analysis 3.0 (CMA 3.0) software to investigate the prevalence of KRAS and BRAF mutations among patients with CRC in Asia. Results. The meta-analysis comprises of 25,525 sample sizes from Asia with most being male 15,743/25525 (61.7%). Overall prevalence of KRAS mutations was (59/88) 36.3% (95% CI: 34.5-38.2) with I 2 = 85.54 % ( P value < 0.001). In 43/59 studies, frequency of KRAS mutations was majorly in codon 12 (76.6% (95% CI: 74.2–78.0)) and less in codon 13 (21.0% (95% CI: 19.1-23.0)). Overall prevalence of BRAF mutations was 5.6% (95% CI: 3.9-8.0) with I 2 = 94.00 % ( P value < 0.001). When stratified according to location, a higher prevalence was observed in Indonesia (71.8%) while Pakistan has the lowest (13.5%). Conclusion. Total prevalence of KRAS and BRAF mutations in CRC was 36.6% and 5.6%, respectively, and the results conformed with several published studies on KRAS and BRAF mutations.

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A study of BRAF mutation in colorectal carcinoma in Indian population

Cited by 4 publications

References 17 publications

The Prevalence of BRAF, PIK3CA, and RAS Mutations in Indian Patients with Colorectal Cancer

The Prevalence of BRAF, PIK3CA, and RAS Mutations in Indian Patients with Colorectal Cancer

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

A Systematic Review and Meta-analysis on the Occurrence of Biomarker Mutation in Colorectal Cancer among the Asian Population

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