Sunagua Aruquipa, M.; D’Alpino Peixoto, R.; Jacome, A.; Cesar, F.; Lorandi, V.; Dienstmann, R. Association of KRAS G12C Status with Age at Onset of Metastatic Colorectal Cancer. Curr. Issues Mol. Biol.2024, 46, 1374-1382.
Sunagua Aruquipa, M.; D’Alpino Peixoto, R.; Jacome, A.; Cesar, F.; Lorandi, V.; Dienstmann, R. Association of KRAS G12C Status with Age at Onset of Metastatic Colorectal Cancer. Curr. Issues Mol. Biol. 2024, 46, 1374-1382.
Sunagua Aruquipa, M.; D’Alpino Peixoto, R.; Jacome, A.; Cesar, F.; Lorandi, V.; Dienstmann, R. Association of KRAS G12C Status with Age at Onset of Metastatic Colorectal Cancer. Curr. Issues Mol. Biol.2024, 46, 1374-1382.
Sunagua Aruquipa, M.; D’Alpino Peixoto, R.; Jacome, A.; Cesar, F.; Lorandi, V.; Dienstmann, R. Association of KRAS G12C Status with Age at Onset of Metastatic Colorectal Cancer. Curr. Issues Mol. Biol. 2024, 46, 1374-1382.
Abstract
Background: The association of age at onset of CRC and prevalence of KRAS G12C mutation is unclear; Methods: Retrospective multicenter study evaluating metastatic CRC patients from January 2019 to July 2023 treated at Oncoclinicas units, tested for tissue-based KRAS/NRAS and BRAF mutations in a centralized genomics lab. Mismatch repair (MMR) status was retrieved from different labs and electronic medical records, as were patient demographics (age, gender) and tumor sidedness. Chi-square test was used to examine the association between clinical and molecular variables, with p value <0.05 being statistically significant; Results: A total of 858 cases were included. The median age was 63.7 years (range 22-95) and 17.4% were less than 50 years old at diagnosis of metastatic CRC. Male patients represented 50.3% of the population. Sidedness distribution was left-side 59.2%, right-side 36.8% and not specified 4%. Prevalence of KRAS mutation was 49.4% and NRAS mutation 3.9%. Among KRAS mutated tumors, the most common variants were G12V (27.6%) and G12D (23.5%), while KRAS G12C was less frequent (6.4%), which represented 3.1% of the overall population. BRAF mutant cases were 7.3%, most commonly V600E. Only 5 (<1%) non-V600E mutations were detected. MSI-high or dMMR was present in 14 cases (1.6%). In the age-stratified analysis, left-sidedness (p<0.001) and KRAS G12C mutation (p=0.046) were associated with younger age (<50 years). In the sidedness-stratified analysis, BRAF mutation (p=0.001) and MSI-high/dMMR status (p=0.009), were more common in right-sided tumors; Conclusions: Our data suggest that KRAS G12C mutations are more frequent in early-onset metastatic CRC. To the best of our knowledge, this is the largest cohort in the Latin American population with mCRC reporting RAS, BRAF and MSI/dMMR status.
Medicine and Pharmacology, Oncology and Oncogenics
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