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KRAS Exon 2 Mutations in Patients with Sporadic Colorectal Cancer: Prevalence Variations in Mexican and Latin American Populations
by
, , , , ,
José Luis Venegas-Rodríguez
1,2,
Jesús Arturo Hernández-Sandoval
1,2,
Melva Gutiérrez-Angulo
1,2,3
,
José Miguel Moreno-Ortiz
1,2,
Anahí González-Mercado
1,2,
Jorge Peregrina-Sandoval
4,
Helen Haydee Fernanda Ramírez-Plascencia
5,
Beatriz Armida Flores-López
6,
Carlos Rogelio Alvizo-Rodríguez
7,
Jesús Alonso Valenzuela-Pérez
8,
Sergio Cervantes-Ortiz
8 and
María de la Luz Ayala-Madrigal
1,2,*
1
Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
2
Programa de Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
3
Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos 47600, Jalisco, Mexico
4
Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan 44600, Jalisco, Mexico
5
Facultad de Medicina, Decanato de Ciencia de la Salud, Universidad Autónoma de Guadalajara, Zapopan 45129, Jalisco, Mexico
6
Departamento de Ciclo de Vida, Facultad de Medicina, Universidad Autónoma de Guadalajara, Zapopan 45129, Jalisco, Mexico
7
Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Puebla 72420, Puebla, Mexico
8
Servicio de Colon y Recto, Hospital Civil “Dr. Juan I. Menchaca”, Guadalajara 44340, Jalisco, Mexico
*
Author to whom correspondence should be addressed.
Cancers 2024, 16(13), 2323; https://doi.org/10.3390/cancers16132323
Submission received: 13 April 2024
/
Revised: 2 June 2024
/
Accepted: 21 June 2024
/
Published: 25 June 2024
(This article belongs to the Special Issue Research Advances in Genetic Variants Associated with Cancer)
Simple Summary
KRAS is one of the most prominent driver genes implicated in colorectal cancer (CRC), with mutations detected in 33% to 50% of CRC patients. Exon 2 harbors up to 98% of these mutations. Variants in this gene play crucial roles in the progression of the disease, influencing its development, clinical manifestations, and treatment election. This study elucidates a 17% prevalence of mutations in KRAS exon 2 among western Mexican patients with sporadic CRC. Furthermore, a 30% pooled prevalence of mutations in KRAS exon 2 was determined after analyzing an additional 16 studies from Latin America, encompassing 12,604 CRC patients. Due to advances in precision medicine treatments, knowing the pathogenic status of the KRAS gene will become imperative to optimally select targeted therapies.
Abstract
We searched for the prevalence of actionable somatic mutations in exon 2 of the KRAS gene in western Mexican patients with CRC. Tumor tissue DNA samples from 150 patients with sporadic CRC recruited at the Civil Hospital of Guadalajara were analyzed. Mutations in exon 2 of the KRAS gene were identified using Sanger sequencing, and the data were analyzed considering clinical–pathological characteristics. Variants in codon 12 (rs121913529 G>A, G>C, and G>T) and codon 13 (rs112445441 G>A) were detected in 26 patients (with a prevalence of 17%). No significant associations were found between these variants and clinical–pathological characteristics (p > 0.05). Furthermore, a comprehensive search was carried out in PubMed/NCBI and Google for the prevalence of KRAS exon 2 mutations in Latin American populations. The 17 studies included 12,604 CRC patients, with an overall prevalence of 30% (95% CI = 0.26–0.35), although the prevalence ranged from 13 to 43% across the different data sources. Determining the variation and frequency of KRAS alleles in CRC patients will enhance their potential to receive targeted treatments and contribute to the understanding of the genomic profile of CRC.
