Influence of Single-Nucleotide Polymorphisms on Clinical Outcomes of Capecitabine-Based Chemotherapy in Colorectal Cancer Patients: A Systematic Review.

Simple Summary: Colorectal cancer is one of the most prevalent neoplasms worldwide. Capecitabine is an oral fluoropyrimidine widely used to treat colorectal cancer in early and advanced stages. However, it shows high interindividual variability in its effectiveness and safety. This variability may be due to genetic variants in proteins involved in the pharmacokinetics and pharmacodynamics of the drug. Currently, only four variants of the DPYD gene are clinically relevant for the prediction of severe toxicity, and there are no validated predictive biomarkers of capecitabine effectiveness. Therefore, the search of potential predictive genetic biomarkers to personalize and optimize capecitabine therapy remains necessary. The aim of this study was to systematically review the literature published in the last 10 years on the influence of single-nucleotide polymorphisms in the main genes involved in capecitabine pharmacokinetics and pharmacodynamics on therapy outcomes in patients with colorectal cancer. The aim of this systematic review was to provide a comprehensive overview of the literature published in the last decade on the association of single-nucleotide polymorphisms in genes involved in the pharmacodynamic and pharmacokinetic pathways of capecitabine with treatment outcomes among colorectal cancer patients. A systematic search of the literature published in the last 10 years was carried out in two databases (Medline and Scopus) using keywords related to the objective. Quality assessment of the studies included was performed using an assessment tool derived from the Strengthening the Reporting of Genetic Association (STREGA) statement. Thirteen studies were included in this systematic review. Genes involved in bioactivation, metabolism, transport, mechanism of action of capecitabine, DNA repair, and folate cycle were associated with toxicity. Meanwhile, genes related to DNA repair were associated with therapy effectiveness. This systematic review reveals that several SNPs other than the four DPYD variants that are screened in clinical practice could have an impact on treatment outcomes. These findings suggest the identification of future predictive biomarkers of effectiveness and toxicity in colorectal cancer patients treated with capecitabine. However, the evidence is sparse and requires further validation. [ABSTRACT FROM AUTHOR]