Thymidylate synthase gene variants as predictors of clinical response and toxicity to fluoropyrimidine-based chemotherapy for colorectal cancer

Castro Rojas, Carlos Andrés y Esparza Mota, Antonio R. y Hernandez Cabrera, Francisco y Romero Díaz, Víktor J. y González Guerrero, Juan Francisco y Maldonado Garza, Héctor Jesús y Garcia Gonzalez, Irma S. y Buenaventura Cisneros, Sergio y Sanchez Lopez, Josefina Y. y Ortiz López, Rocío y Camacho Morales, Alberto y Barboza Quintana, Oralia y Rojas Martínez, Augusto (2017) Thymidylate synthase gene variants as predictors of clinical response and toxicity to fluoropyrimidine-based chemotherapy for colorectal cancer. Drug Metabolism and Personalized Therapy, 32 (4). pp. 208-218. ISSN 2363-8907

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URL o página oficial: http://doi.org/10.1515/dmpt-2017-0028

Resumen

Abstract Background: Fluoropyrimidines form the chemotherapy backbone of advanced and metastatic colorectal cancer (CRC). These drugs are frequently associated with toxicity events that result in dose adjustments and even suspension of the treatment. The thymidylate synthase (TYMS) gene is a potential marker of response and toxicity to fluoropyirimidines as this enzyme is the molecular target of these drugs. Our aim was to assess the association between variants of TYMS with response and toxicity to fluoropyrimidines in patients with CRC in independent retrospective and prospective studies. Methods: Variants namely rs45445694, rs183205964, rs2853542 and rs151264360 of TYMS were genotyped in 105 CRC patients and were evaluated to define their association with clinical response and toxicity to fluoropyrimidines. Additionally, the relationship between genotypes and tumor gene expression was analyzed by quantitative polymerase chain reaction. Results: The 2R/2R (rs45445694) was associated with clinical response (p = 0.05, odds ratio (OR) = 3.45) and severe toxicity (p = 0.0014, OR = 5.21, from pooled data). Expression analysis in tumor tissues suggested a correlation between the 2R/2R genotype and low TYMS expression. Conclusions: The allele 2R (rs45445694) predicts severe toxicity and objective response in advanced CRC patients. In addition, the alleles G(rs2853542) and 6bp-(rs151264360) are independent predictors of response failure to chemotherapy. This is the first study made on a Latin American population that points out TYMS gene variants have predictive values for response and toxicity in patients with CRC treated with fluoropyrimidine-based chemotherapy.

Tipo de elemento: Article
Divisiones: Medicina
Usuario depositante: Lic. Josimar Pulido
Creadores:
CreadorEmailORCID
Castro Rojas, Carlos AndrésNO ESPECIFICADONO ESPECIFICADO
Esparza Mota, Antonio R.NO ESPECIFICADONO ESPECIFICADO
Hernandez Cabrera, FranciscoNO ESPECIFICADONO ESPECIFICADO
Romero Díaz, Víktor J.NO ESPECIFICADONO ESPECIFICADO
González Guerrero, Juan FranciscoNO ESPECIFICADONO ESPECIFICADO
Maldonado Garza, Héctor JesúsNO ESPECIFICADONO ESPECIFICADO
Garcia Gonzalez, Irma S.NO ESPECIFICADONO ESPECIFICADO
Buenaventura Cisneros, SergioNO ESPECIFICADONO ESPECIFICADO
Sanchez Lopez, Josefina Y.NO ESPECIFICADONO ESPECIFICADO
Ortiz López, RocíoNO ESPECIFICADONO ESPECIFICADO
Camacho Morales, AlbertoNO ESPECIFICADONO ESPECIFICADO
Barboza Quintana, OraliaNO ESPECIFICADONO ESPECIFICADO
Rojas Martínez, AugustoNO ESPECIFICADONO ESPECIFICADO
Fecha del depósito: 01 Mayo 2020 15:56
Última modificación: 08 Jun 2020 21:38
URI: http://eprints.uanl.mx/id/eprint/17427

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