Tohoku J. Exp. Med., 2019 November, 249(3)

Genetic Polymorphisms in APC, DVL2, and AXIN1 Are Associated with Susceptibility, Advanced TNM Stage or Tumor Location in Colorectal Cancer

MÓNICA ALEJANDRA ROSALES-REYNOSO,¹ ANILÚ MARGARITA SAUCEDO-SARIÑANA,¹ KARLA BERENICE CONTRERAS-DÍAZ,¹ ROSA MARÍA MÁRQUEZ-GONZÁLEZ,¹ PATRICIO BARROS-NÚÑEZ,² TOMÁS DANIEL PINEDA-RAZO,³ MARÍA EUGENIA MARIN-CONTRERAS,⁴ SCAR DURÁN-ANGUIANO,⁵ MARTHA PATRICIA GALLEGOS-ARREOLA,⁶ SILVIA ESPERANZA FLORES-MARTÍNEZ¹ and JOSÉ SÁNCHEZ-CORONA¹

¹Molecular Medicine Division, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico
²Research Unit of Metabolic Diseases, Pediatric UMAE, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico
³Medical Oncology Service, Specialty Hospital, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico
⁴Gastroenterology Service, Specialty Hospital, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico
⁵Coloproctology Service, Specialty Hospital, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico
⁶Genetic Division, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico

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/β-catenin pathway regulating the level of β-catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of β-catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the β-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.

Keywords —— colorectal cancer; destruction complex; haplotype; polymorphism; Wnt/β-catenin

© 2019 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2019, 249, 173-183

Correspondence: Mónica Alejandra Rosales-Reynoso, Ph.D., División de Medicina Molecular. Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada # 800, Colonia Independencia, Guadalajara, Jalisco CP 44340, México.

e-mail: mareynoso77@yahoo.com.mx; monica.rosales@imss.gob.mx