Association of the rs8720 and rs12587 KRAS Gene Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico

rs8720 和 rs12587 KRAS 基因变异与墨西哥人群结肠直肠癌的关联及其计算机分析

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作者:Martha Patricia Gallegos-Arreola, Asbiel Felipe Garibaldi-Ríos, José Israel Cruz-Sánchez, Luis Eduardo Figuera, Carlos Alberto Ronquillo-Carreón, Mónica Alejandra Rosales-Reynoso, Belinda Claudia Gómez-Meda, Irving Alejandro Carrillo-Dávila, Ana María Puebla-Pérez, Héctor Montoya-Fuentes, Valeria Pe

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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