Background: Childhood cancers represent a heterogeneous group of malignancies and remain one of the leading causes of mortality among children under 14 years of age, ranking second only to accidental injuries, and fourth among individuals aged 15 to 19 years. Despite notable improvements in cure rates, a substantial proportion of patients experience acute or long-term toxicities associated with treatment. Methotrexate (MTX), a chemotherapeutic agent, has been employed effectively for over six decades in the management of pediatric malignancies. High-dose methotrexate constitutes a cornerstone of pediatric cancer therapy; however, its clinical utility is frequently constrained by dose-limiting toxicities. Objectives: This study investigates the impact of genetic polymorphisms in genes involved in nucleotide metabolism, as well as methotrexate and folate metabolic pathways, on treatment-related toxicity in childhood cancer. Methods: Using real-time polymerase chain reaction, 14 polymorphisms across 12 genes were analyzed in a cohort of 107 patients. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events v. 5.0. Results: Multivariate logistic regression analysis revealed that the male sex (p = 0.3) and the AA genotype of MTHFD1 rs2236225 were associated with grade III–IV gastrointestinal toxicity (p = 0.03), while the A allele of MTHFR rs1801133 and the AA genotype of GSTP1 rs1695 were associated with grade I–IV hematologic toxicity (p < 0.01 and p = 0.02, respectively). Conclusions: High-dose methotrexate (HDMTX) is a critical agent in the treatment of childhood cancers. Our findings suggest that genetic polymorphisms within methotrexate and folate metabolic pathways may serve as potential predictive biomarkers of treatment-related toxicity.

Cancer is the leading cause of disease-related death among children. Vincristine (VCR), a key component of childhood cancer treatment protocols, is associated with the risk of peripheral neuropathy (PN), a condition that may be reversible upon drug discontinuation but can also leave lasting sequelae. Single nucleotide polymorphism (SNP) in genes involved in VCR pharmacokinetics and pharmacodynamics have been investigated in relation to an increased risk of PN. However, the results of these studies have been inconsistent. A retrospective cohort study was conducted to investigate the potential association of drug transporter genes from the ATP-binding cassette (ABC) family and the centrosomal protein 72 (CEP72) gene with the development of PN in 88 Caucasian children diagnosed with cancer and treated with VCR. Genotyping was performed using real-time PCR techniques for the following SNPs: ABCB1 rs1128503, ABCC1 rs246240, ABCC2 rs717620, and CEP72 rs924607. The results indicated that age at diagnosis (OR = 1.33; 95% CI = 1.07–1.75) and the ABCC1 rs246240 G allele (OR = 12.48; 95% CI = 2.26–100.42) were associated with vincristine-induced peripheral neuropathy (VIPN). No association was found between this toxicity and CEP72 rs924607. Our study provides insights that may contribute to optimizing childhood cancer therapy in the future by predicting the risk of VIPN

Cardiovascular diseases (CVDs) constitute a major global health problem, being the leading cause of death. Several risk factors for CVDs have been identified, including tobacco use, unhealthy diet, and physical inactivity. However, the role of genetic factors in CVDs remains unclear. Recent studies suggest that vitamin D deficiency is associated with an increased risk of CVDs. Therefore, the aim of this study is to assess the impact of 13 single nucleotide polymorphisms (SNPs) located in genes involved in vitamin D metabolism (VDR, GC, CYP27B1, CYP2R1, and CYP24A1) on the risk of developing CVDs. A retrospective case-control study was conducted in 766 Caucasian individuals from southern Spain: 383 diagnosed with CVDs and 383 without cardiovascular complications, matched based on age and sex. The 13 SNPs were identified by real-time PCR using TaqMan™ probes at the Virgen de las Nieves University Hospital and the University of Granada. According to statistical analysis the allele G and genotype GG of the SNP CYP2R1 rs10741657 and the allele C and CC genotype of the SNP CYP27B1 rs3782130 are associated with a decreased risk of CVDs and diabetes in three of the five heritage models studied. Thus, it can be concluded that CYP2R1 rs10741657 and CYP27B1 rs3782130 could be used as risk biomarkers for CVDs in the future, although studies with a larger number of participants are needed.