Association of KRAS G12C status with age at onset of metastatic colorectal cancer in the Brazilian population: A multicenter analysis of a molecular profile database (RAS, BRAF and MSI status).

Abstract

173 Background: Precision oncology has changed clinical practice in metastatic colorectal cancer (mCRC). However, there is little data about molecular epidemiology of mCRC in Brazil. Our study aims to create a nation-wide database to develop future projects in the Oncoclinicas Group. Methods: This was an observational, retrospective, and multicenter study. Anonymized medical records of adult patients (18 years or older) with mCRC from January 2019 to July 2023 were reviewed. All specimens were centrally reviewed in our laboratory (all tissue-based analysis). Demographic data included age, gender, region of origin and sidedness. Molecular data included RAS, BRAF and MMR status. Descriptive statistics, frequencies and percentages were used for categorical variables, while mean and medians for numerical variables. The correlation between variables was analyzed through Chi-square and T-test (when applicable). Significance for all results was established as a p value of < 0.05. The statistical software used was SPSS. Results: A total of 858 cases were included. Median age was 63.7 y/o (range 22-95) and 11.9% were < 45 y/o. Male patients represented 50.3% of the population and 76.1% were from the Southeast region. Left-sided tumors comprised 59.2% of the cases, 36.8% were right-sided and 4% were not specified. Wild-type KRAS corresponded to 46.7% of the total cases, while 49.4% were KRAS mutant and 3.9% NRAS mutant. The most common KRAS mutations were G12V (27.6%) and G12D (23.5%). KRAS G12C mutation was found in 6.4% of all KRAS mutant tumors. The most common NRAS mutation was the Q61K (24.2%). Only 7.3% of cases were BRAF mutated, most of them V600E, only 5 non-V600E mutations were detected. MSI-high was present in 14 cases only (1.6%). In the age-stratified analysis, left-sidedness (p=0.001) and KRAS G12C mutation (p=0.016) were associated with younger age (<45 y/o). In the sidedness-stratified analysis, younger age (p=0.001), BRAF mutation (p=0.001) and MSI-high status (p=0.009), were more common in right-sided tumors. Conclusions: In our Brazilian cohort of mCRC patients, frequencies of RAS and BRAF mutations were similar to worldwide data. However, we found lower than expected frequency of MSI-high tumors. KRAS G12C mutation was associated with early-onset mCRC, an emergent population in which KRAS G12C inhibitors might be particulary useful. To the best of our knowledge, this is the largest cohort in the Brazilian population with mCRC reporting RAS, BRAF and MSI status. Larger studies are needed to confirm these findings.