Colorectal Cancers from Distinct Ancestral Populations Show Variations in BRAF Mutation Frequency

Abstract

It has been demonstrated for some cancers that the frequency of somatic oncogenic mutations may vary in ancestral populations. To determine whether key driver alterations might occur at different frequencies in colorectal cancer, we applied a high-throughput genotyping platform (OncoMap) to query 385 mutations across 33 known cancer genes in colorectal cancer DNA from 83 Asian, 149 Black and 195 White patients. We found that Asian patients had fewer canonical oncogenic mutations in the genes tested (60% vs Black 79% (P = 0.011) and White 77% (P = 0.015)), and that BRAF mutations occurred at a higher frequency in White patients (17% vs Asian 4% (P = 0.004) and Black 7% (P = 0.014)). These results suggest that the use of genomic approaches to elucidate the different ancestral determinants harbored by patient populations may help to more precisely and effectively treat colorectal cancer.

FrequentBRAFmutation in early-onset colorectal cancer in Taiwan: association with distinct clinicopathological and molecular features and poor clinical outcome

“…The difference could not be explained by the methodology, as the same method was used and similar overall BRAF mutation rates have been reported in other Asian populations 26 27. Considering that CRCs in Asians may have a lower BRAF mutation rate than those in white patients,28 EOCRCs in Taiwan are particularly prone to this molecular alteration.…”

Immunohistochemical detection of the BRAF V600E mutant protein in colorectal cancers in Taiwan is highly concordant with the molecular test

“…The finding is consistent with previous reports from Taiwan (3.8–5.8%) and similar to the reports of other Asian countries (1.7–9%) . In an ethnicity‐based study by Hanna MC et al ., the frequency of BRAF mutations in CRCs has been shown to be significantly different between Asian (4%) and Caucasian populations (17%), while mutations in other cancer genes such as APC , CTNNB1 , KRAS , NRAS , PIK3CA and TP53 show no difference . The BRAF mutation has been proposed to be the earliest event in the microsatellite instability pathway of colon cancer carcinogenesis .…”

“…[33][34][35][36][37] In an ethnicity-based study by Hanna MC et al, the frequency of BRAF mutations in CRCs has been shown to be significantly different between Asian (4%) and Caucasian populations (17%), while mutations in other cancer genes such as APC, CTNNB1, KRAS, NRAS, PIK3CA and TP53 show no difference. 38 The BRAF mutation has been proposed to be the earliest event in the microsatellite instability pathway of colon cancer carcinogenesis. 39 The lower BRAF mutation rates indicated that colorectal cancers are involved infrequently in this pathway among Asians.…”

Racial disparity in metabolic regulation of cancer

“…In another study conducted on colorectal cancer, it was discovered that a lower mutational load appeared in Asians compared to African-Americans and Caucasians (60% vs. 79 & 77%) upon investigation of 385 mutations across 33 known cancer genes. BRAF mutations were more prevalent in Caucasians, with the highest frequency observed for the BRAF V600E mutation (130). …”