Association of the rs8720 and rs12587 KRAS Gene Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico
Author:
Gallegos-Arreola Martha Patricia1ORCID, Garibaldi-Ríos Asbiel Felipe12, Cruz-Sánchez José Israel34ORCID, Figuera Luis Eduardo12ORCID, Ronquillo-Carreón Carlos Alberto34, Rosales-Reynoso Mónica Alejandra5, Gómez-Meda Belinda Claudia6ORCID, Carrillo-Dávila Irving Alejandro12, Puebla-Pérez Ana María7, Montoya-Fuentes Héctor5, Peralta-Leal Valeria8, Zúñiga-González Guillermo M.5ORCID
Affiliation:
1. División de Genética, Centro de Investigación Biomédica de Occidente (CIBO), Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico 2. Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico 3. Especialidad en Oncología Médica, Universidad de Guadalajara (UdeG)/UMAE Hospital de Especialidades, Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico 4. Oncología Clínica, UMAE Hospital de Especialidades, Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44329, Jalisco, Mexico 5. División de Medicina Molecular, Centro de Investigación Biomédica de Occidente (CIBO), Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, Guadalajara 44340, Jalisco, Mexico 6. Departamento de Biología Molecular y Genómica, Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico 7. Laboratorio de Inmunofarmacología, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara (UdeG), Guadalajara 44430, Jalisco, Mexico 8. Facultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros, Universidad Autónoma de Tamaulipas, Ciudad Victoria 87300, Tamaulipas, Mexico
Abstract
Colorectal cancer (CRC) is a major global health challenge and one of the top 10 cancers in Mexico. Lifestyle and genetic factors influence CRC development, prognosis, and therapeutic response; identifying risk factors, such as the genes involved, is critical to understanding its behavior, mechanisms, and prognosis. The association between KRAS gene variants (rs8720 and rs12587) and CRC in the Mexican population was analyzed. We performed in silico analysis and analyzed 310 healthy individuals and 385 CRC patients using TaqMan assays and real-time PCR. The CC and GG genotypes of rs8720 and rs12587 were identified as CRC risk factors (p < 0.05). The CC and TC genotypes of the rs8720 were associated with rectal cancer, age over 50 years, moderately differentiated histology, and advanced cancer stage. TG and GG genotypes of the rs12587 variant were a risk factor in the CRC group, in patients with stage I–II, males, and stage III–IV non-chemotherapy response. The TG haplotype is protected against CRC. The combined CCGG genotype was linked to CRC risk. In silico analysis revealed that the rs12587 and rs8720 variants could influence KRAS gene regulation via miRNAs. In conclusion, rs8720 and rs12587 variants of the KRAS gene were associated with CRC risk and could influence KRAS regulation via miRNAs.
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