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- Title
Genetic Polymorphisms in APC, DVL2, and AXIN1 Are Associated with Susceptibility, Advanced TNM Stage or Tumor Location in Colorectal Cancer.
- Authors
Rosales-Reynoso, Mónica Alejandra; Saucedo-Sariñana, Anilú Margarita; Contreras-Díaz, Karla Berenice; Márquez-González, Rosa María; Barros-Núñez, Patricio; Pineda-Razo, Tomás Daniel; Marin-Contreras, María Eugenia; Durán-Anguiano, Óscar; Gallegos-Arreola, Martha Patricia; Flores-Martínez, Silvia Esperanza; Sánchez-Corona, José
- Abstract
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. The named "destruction complex" has a critical function in the Wnt/ß -catenin pathway regulating the level of ß -catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of ß -catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the ß -catenin destruction complex to develop CRC, specifically adenomatous polyposis coli (APC) (rs11954856 G>T and rs459552 A>T), axis inhibition protein 1 (AXIN1) (rs9921222 C>T and rs1805105 C>T), AXIN2 (rs7224837 A>G), and dishevelled 2 (DVL2) (2074222 G>A and rs222836 C>T). Genomic DNA from 180 sporadic colorectal cancer patients and 150 healthy blood donors were analyzed. The identification of polymorphisms was made by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. Increased susceptibility to CRC was associated with the polymorphic variants rs11954856 (APC), rs222836 (DVL2), and rs9921222 (AXIN1). Decreased susceptibility was associated with the polymorphisms rs459552 (APC) and 2074222 (DVL2). Association was also observed with advanced Tumor-Node-Metastasis (TNM) stages and tumor location. The haplotypes G-T in APC (rs11954856-rs459552) and A-C in DVL2 (rs2074222-rs222836) were associated with decreased risk of CRC, while the G-T haplotype in the DVL2 gene was associated with increased CRC risk. In conclusion, our results suggest that variants in the destruction complex genes may be involved in the promotion or prevention of colorectal cancer.
- Subjects
COLORECTAL cancer; ADENOMATOUS polyposis coli; TUMOR classification; RESTRICTION fragment length polymorphisms; GENETIC polymorphisms
- Publication
Tohoku Journal of Experimental Medicine, 2019, Vol 249, Issue 3, p173
- ISSN
0040-8727
- Publication type
Article
- DOI
10.1620/tjem.249.173