Role of Single-Nucleotide Polymorphisms in Genes Implicated in Capecitabine Pharmacodynamics on the Effectiveness of Adjuvant Therapy in Colorectal Cancer
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 pharma...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/25/1/104 |
| Summary: | 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 <i>TYMS</i>, <i>ENOSF1</i>, <i>MTHFR</i>, <i>ERCC1</i>/<i>2</i>, and <i>XRCC1</i>/<i>3</i> genes were genotyped in 142 CRC patients using real-time PCR with predesigned TaqMan<sup>®</sup> probes. A significant association was found between favorable DFS and the <i>ENOSF1</i> rs2612091-T allele (<i>p</i> = 0.010; HR = 0.34; 95% CI = 0.14–0.83), as well as with the <i>TYMS</i>/<i>ENOSF1</i> region ACT haplotype (<i>p</i> = 0.012; HR = 0.37; 95% CI = 0.17–0.80). Other factors such as low histological grade (<i>p</i> = 0.009; HR = 0.34; 95% CI = 0.14–0.79) and a family history of cancer (<i>p</i> = 0.040; HR = 0.48; 95% CI = 0.23–0.99) were also linked to improved DFS. Therefore, the SNP <i>ENOSF1</i> rs2612091 could be considered as a predictive genetic biomarker for survival in CRC patients receiving capecitabine-based adjuvant regimens. |
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| ISSN: | 1661-6596 1422-0067 |