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墨西哥人群中rs1966265和rs351855基因变异与结直肠癌的关联及其计算机模拟分析

Association of the rs1966265 and rs351855 Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico.

作者信息

Carrillo-Dávila Irving Alejandro, Garibaldi-Ríos Asbiel Felipe, Figuera Luis E, Gómez-Meda Belinda Claudia, Zúñiga-González Guillermo M, Puebla-Pérez Ana María, García-Verdín Patricia Montserrat, Castro-García Paola Beatriz, Gutiérrez-Hurtado Itzae Adonai, Torres-Mendoza Blanca Miriam, Gallegos-Arreola Martha Patricia

机构信息

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.

Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico.

出版信息

Biomedicines. 2024 Mar 7;12(3):602. doi: 10.3390/biomedicines12030602.

Abstract

The aim of this study was to associate rs1966265 and rs351855 variants with colorectal cancer (CRC) in a Mexican population and to perform in silico analysis. Genomic DNA from 412 healthy individuals and 475 CRC patients was analyzed. In silico analysis was performed using the PolyPhen-V2, GEPIA, GTEx, and Cytoscape platforms. The GA genotype dominant model (GAAA) of rs1966265 and the AA genotype dominant and recessive models of rs351855 were identified as CRC risk factors ( < 0.05). CRC patients aged ≥ 50 years at diagnosis who consumed alcohol had a higher incidence of the rs351855 GA genotype than the control group ( < 0.05). Associations were observed between the rs1966265 GA genotype and patients with rectal cancer and stage III-IV disease. The rs351855 AA genotype was a risk factor for partial chemotherapy response, and the GA + AA genotype for age ≥ 50 years at diagnosis and rectal cancer was associated with a partial response to chemotherapy ( < 0.05). The AA haplotype was associated with increased susceptibility to CRC. In silico analysis indicated that the rs351855 variant is likely pathogenic (score = 0.998). Genotypic expression analysis in blood samples showed statistically significant differences ( < 0.05). , , and share signaling pathways with . Therefore, rs1966265 and rs351855 may be potential CRC risk factors.

摘要

本研究旨在探讨墨西哥人群中rs1966265和rs351855基因变异与结直肠癌(CRC)的关系,并进行计算机模拟分析。分析了412名健康个体和475名CRC患者的基因组DNA。使用PolyPhen-V2、GEPIA、GTEx和Cytoscape平台进行计算机模拟分析。rs1966265的GA基因型显性模型(GAAA)和rs351855的AA基因型显性及隐性模型被确定为CRC危险因素(P<0.05)。诊断时年龄≥50岁且饮酒的CRC患者中,rs351855 GA基因型的发生率高于对照组(P<0.05)。观察到rs1966265 GA基因型与直肠癌患者及III-IV期疾病之间存在关联。rs351855 AA基因型是部分化疗反应的危险因素,诊断时年龄≥50岁且患有直肠癌的GA+AA基因型与化疗部分反应相关(P<0.05)。AA单倍型与CRC易感性增加相关。计算机模拟分析表明,rs351855变异可能具有致病性(评分=0.998)。血样中的基因型表达分析显示出统计学上的显著差异(P<0.05)。 、 和 与 共享信号通路。因此,rs1966265和rs351855可能是潜在的CRC危险因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21f8/10968131/cfa714543149/biomedicines-12-00602-g001.jpg

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