Association of Variants in IL-1RN (rs2234663) and IL-1β (rs1143627, rs16944) and Interleukin-1β Levels with Colorectal Cancer: Experimental Study and In Silico Analysis

• Published in: Genes 2024-11, Vol.15 (12), p.1528
• Main Authors: Gallegos-Arreola, Martha Patricia, Asbiel Felipe Garibaldi-Ríos, Gutiérrez-Hurtado, Itzae Adonaí, Zúñiga-González, Guillermo Moisés, Figuera, Luis E, Gómez-Meda, Belinda Claudia, Puebla-Pérez, Ana María, José Elías García-Ortiz, Delgado-Saucedo, Jorge I, Castro-García, Paola Beatriz, María de Jesús Rentería-Ramírez, Torres-Mendoza, Blanca Miriam
• Format: Article
• Language: English
• Subjects: Alleles; Colorectal cancer; Colorectal carcinoma; Cytokines; Enzymes; Gene regulation; Genes; Genotype & phenotype; Genotypes; Hemorrhoids; IL-1β; Inflammation; Inflammatory diseases; Interleukin 1 receptors; Interleukins; Metastases; mRNA; Risk factors; Sociodemographics
• ISSN: 2073-4425
• DOI: 10.3390/genes15121528

Background/Objectives. Colorectal cancer (CRC) is a multifactorial disease where the inflammatory state is crucial. This study analyzes the association of the IL-1RN (rs2234663) and IL-1β (rs1143627, rs16944) variants and IL-1β levels with CRC. Methods. This study included 230 CRC patients and 256 controls. Genotypes were determined by PCR and plasma IL-1β levels by ELISA. RegulomeDB analyzed the variants’ functional impacts, while OncoDB assessed IL-1β and IL-1RN expression’s influence on CRC. Results. The A1A1 genotype and dominant pattern of the rs2234663 variant were risk factors for CRC, whereas the A1A2 genotype showed a protective effect. The TC genotype of the rs1143627 variant and the T allele of rs16944 were associated with increased risk, whereas the C allele had a protective effect. The A1A1 genotype was associated with stage I–II CRC diagnosis, while the A2A2 genotype was associated with stage III–IV and ethanol consumption. The CC genotype of rs1143627 was associated with people younger than 50 years and tobacco use, and the TCCC genotype was related to stage III–IV stages and metastasis and hemorrhoids (p < 0.05). IL-1β levels were not associated with CRC. In silico analysis revealed that the variants are in located in important regions regulatory of genes. Elevated IL-1B and IL-1RN mRNA levels were found in CRC, linked to clinicopathological features of the disease. Conclusions. The analyzed variants are associated with CRC and may influence gene regulation by being located at critical sites of key genetic regulators.