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Arch Iran Med. 2019;22(8):453-460.
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  PDF Download: 64

Original Article

GSK3β Polymorphisms Are Associated with Tumor Site and TNM Stage in Colorectal Cancer

Mónica Alejandra Rosales-Reynoso 1 * , Paulette Zepeda-López 1, Anilú Margarita Saucedo-Sariñana 1, Tomas Daniel Pineda-Razo 2, Patricio Barros-Núñez 3, Martha Patricia Gallegos-Arreola 4, Silvia Esperanza Flores-Martínez 1, José Sánchez-Corona 1

1 Molecular Medicine Division, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico
2 Medical Oncology Service, Specialty Hospital, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico
3 Research Unit of Metabolic Diseases, Pediatric Hospital, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico
4 Genetic Division, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico

Abstract

Background: Mutations and polymorphisms of the GSK3β gene have been associated with several diseases including Alzheimer disease, diabetes and cancer; however, to date, no variants of this gene have been associated with colorectal cancer (CRC). This study aims to explore, for the first time, the association of the GSK3β rs334558 and rs6438552 polymorphisms with CRC.

Methods: Genomic DNA from 330 CRC patients and healthy blood donors were analyzed. Identification of polymorphisms was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test.

Results: Patients carrying the C/T genotype for the rs334558 (T>C) polymorphism showed an increased risk for CRC (OR = 1.71, 95% CI: 1.05–2.79, P = 0.039); this association was also observed for TNM stage and tumor location. For the rs6438552 (T>C) polymorphism, the OR analysis showed that patients carrying C/T and C/C genotypes have a decreased risk for CRC (OR = 0.44, 95% CI: 0.27–0.70, P = 0.001 and OR = 0.24, 95% CI: 0.10–0.64, P = 0.001, respectively); this decreased risk was also evident in the stratified analysis by TNM stage and tumor location. Haplotype analysis of these 2 loci of GSK3β (rs334558 and rs6438552) showed differential distribution. The T-T and C-C haplotype was associated with a decreased risk of CRC, while the T-C haplotype was associated with an increased risk of CRC.

Conclusion: Our results denote that GSK3β gene polymorphisms play a significant role in promoting or preventing CRC. Additionally, variations in this gene are associated with the tumor site and the tumor-node-metastasis (TNM) stage in these patients.

Keywords: Colorectal cancer, GSK3β gene, GSK3β polymorphisms, GSK3β haplotypes
Cite this article as: Rosales-Reynoso MA, Zepeda-López P, Saucedo-Sariñana AM, Pineda-Razo TD, Barros-Núñez P, GallegosArreola MP, et al. GSK3β polymorphisms are associated with tumor site and TNM stage in colorectal cancer. Arch Iran Med. 2019;22(8):453–460.
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Submitted: 12 Jan 2019
Accepted: 16 Apr 2019
First published online: 01 Aug 2019
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