Role of Single-Nucleotide Polymorphisms in Genes Implicated in Capecitabine Pharmacodynamics on the Effectiveness of Adjuvant Therapy in Colorectal Cancer

Author:

Cura Yasmin1ORCID,Sánchez-Martín Almudena1,Márquez-Pete Noelia1,González-Flores Encarnación23,Martínez-Martínez Fernando4ORCID,Pérez-Ramírez Cristina5,Jiménez-Morales Alberto1

Affiliation:

1. Pharmacy Service, Pharmacogenetics Unit, University Hospital Virgen de las Nieves, 18014 Granada, Spain

2. Medical Oncology, University Hospital Virgen de las Nieves, 18014 Granada, Spain

3. Biomedical Research Institute—ibs.Granada, 18012 Granada, Spain

4. Pharmaceutical Care Research Group, Pharmacy Faculty, University of Granada, 18016 Granada, Spain

5. Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, 18016 Granada, Spain

Abstract

Colorectal cancer (CRC) is a highly prevalent form of neoplasm worldwide. Capecitabine, an oral antimetabolite, is widely used for CRC treatment; however, there exists substantial variation in individual therapy response. This may be due to genetic variations in genes involved in capecitabine pharmacodynamics (PD). In this study, we investigated the role of single-nucleotide polymorphisms (SNPs) related to capecitabine’s PD on disease-free survival (DFS) in CRC patients under adjuvant treatment. Thirteen SNPs in the TYMS, ENOSF1, MTHFR, ERCC1/2, and XRCC1/3 genes were genotyped in 142 CRC patients using real-time PCR with predesigned TaqMan® probes. A significant association was found between favorable DFS and the ENOSF1 rs2612091-T allele (p = 0.010; HR = 0.34; 95% CI = 0.14–0.83), as well as with the TYMS/ENOSF1 region ACT haplotype (p = 0.012; HR = 0.37; 95% CI = 0.17–0.80). Other factors such as low histological grade (p = 0.009; HR = 0.34; 95% CI = 0.14–0.79) and a family history of cancer (p = 0.040; HR = 0.48; 95% CI = 0.23–0.99) were also linked to improved DFS. Therefore, the SNP ENOSF1 rs2612091 could be considered as a predictive genetic biomarker for survival in CRC patients receiving capecitabine-based adjuvant regimens.

Funder

Instituto de Salud Carlos III

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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