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Variation in KRAS/NRAS/BRAF-Mutation Status by Age, Sex, and Race/Ethnicity Among a Large Cohort of Patients with Metastatic Colorectal Cancer (mCRC)
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Variation in KRAS/NRAS/BRAF-Mutation Status by Age, Sex, and Race/Ethnicity Among a Large Cohort of Patients with Metastatic Colorectal Cancer (mCRC)
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Variation in KRAS/NRAS/BRAF-Mutation Status by Age, Sex, and Race/Ethnicity Among a Large Cohort of Patients with Metastatic Colorectal Cancer (mCRC)
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Journal Article
Variation in KRAS/NRAS/BRAF-Mutation Status by Age, Sex, and Race/Ethnicity Among a Large Cohort of Patients with Metastatic Colorectal Cancer (mCRC)
2024
Overview
Background
Racial/ethnic disparities in metastatic colorectal cancer (mCRC) survival are well documented as is the impact that tumor mutation of
KRAS
and
BRAF
has on prognosis. It has been suggested that frequency differences of
KRAS-
and
BRAF-
mutated tumors may partially explain this disparity. Demographic differences in mutation frequency are not well established nor whether mutation and microsatellite instability (MSI) differentially impact survival among groups.
Methods
Using data for 11,117 patients diagnosed with de-novo mCRC from an electronic health record-derived database we estimated adjusted odds ratios (aOR) to characterize the association between demographics and MSI and
KRAS/NRAS/BRAF
-mutation status. Stratified Cox models were used to identify differences in overall survival (OS), adjusting for treatment and demographics.
Results
Being female, compared to male, (aOR
KRAS
:1.33 (1.23–1.44); aOR
BRAF
:1.84 (1.56–2.16)), and non-Hispanic Black race (NHB), compared to non-Hispanic White (NHW) (aOR
KRAS
:1.62 (1.42–1.85); aOR
BRAF
: 0.55 (0.38–0.77)) were associated with
KRAS-
or
BRAF-
mutant tumors. MSI prevalence was similar across race/ethnicity but higher in women.
BRAF-
mutant tumors were associated with poorer prognosis overall, especially among non-white patients. Among patients who had
KRAS/NRAS/BRAF-
WT tumors we observed no difference in OS by race or MSI. Among patients with
KRAS
-mutant tumors, Hispanic patients had more favorable prognosis adjusted hazards ratio (aHR) = 0.76 (0.65–0.89)) than their NHW counterparts. Among those with
BRAF-
mutant tumors, NHB patients had poorer prognosis than NHW patients (aHR:1.78 (1.08–2.93)).
Conclusion
MSI and frequency of
KRAS
and
BRAF
mutations differed by demographics. Racial/ethnic disparities in OS differed by mutation. Future studies should explore biological and/or social determinants underlying these differences.
Publisher
Springer US,Springer Nature B.V
Subject
/ Aged
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - mortality
/ Colorectal Neoplasms - pathology
/ Ethnicity - statistics & numerical data
/ Female
/ GTP Phosphohydrolases - genetics
/ Humans
/ Male
/ Medicine
/ Mutation
/ Oncology
/ Proto-Oncogene Proteins B-raf - genetics
/ Proto-Oncogene Proteins p21(ras) - genetics
/ White
