Yuri Giovanna Vanessa Trujillo-Fernández
1,2 , Carmen Yzabal-Barbedillo
1, Anilú Margarita Saucedo-Sarinaña
3 , César de Jesús Tovar-Jácome
1, Miriam Yadira Godínez-Rodríguez
1, Patricio Barros-Núñez
2 , Martha Patricia Gallegos-Arreola
4 , Clara Ibet Juárez-Vázquez
3, Tomás Daniel Pineda-Razo
5 , María Eugenia Marín-Contreras
6 , Mónica Alejandra Rosales-Reynoso
1* 1 Molecular Medicine Division, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
2 Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México
3 Department of Devices and Systems I, Facultad de Medicina. Decanato Ciencias de la Salud, Universidad Autónoma de Guadalajara (UAG). Zapopan, Jalisco, México
4 Genetic Division, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
5 Medical Oncology Service, Hospital de Especialidades, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
6 Gastroenterology Service, Hospital de Especialidades, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
Abstract
Background: miRNAs are non-coding RNAs participating actively in the post-translational regulation of oncogenes, tumor suppressor, and DNA repair genes implicated in colorectal cancer (CRC). This study aims to examine the association of the variants miR-27a (rs895819 A>G), miR-196a2 (rs11614913 T>G) and miR-146a (rs2910164 C>G) in Mexican CRC patients.
Methods: DNA samples from 183 patients and 186 healthy Mexican subjects were analyzed. Variants were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) and adjusted by the Bonferroni test.
Results: Patients carrying the G/G genotype of the rs895819 variant in the miR-27a gene showed an increased risk of CRC (19% vs 12%, P=0.013). A similar tendency was noticed for patients younger than 50 years carrying A/G (48% vs 41%, P=0.014). The A/G genotype in TNM stages I+II (55.7% vs 40.8%, P=0.011) and tumor location in the colon (69.5 vs 40.8%, P=0.001) were also increased. For the variant rs11614913 of the miR-196a2 gene, carriers of the C/C genotype showed an increased risk of CRC (32% vs 22%, P=0.009). This genotype was more frequent in TNM stage III+IV (36.8% vs 22.5%, P=0.007) and the tumor had a more recurrent location in the rectum (31.6% vs 22.5%, P=0.013). The rs2910164 variant of the miR-146a gene was found to have no significant risk associations.
Conclusion: Our results reveal that the rs895819 variant in miR-27a and rs11614913 in miR-196a2 have a substantial impact on the development of CRC.