Centrosomal protein72 rs924607 and vincristine-induced Neuropathy in Pediatric Acute Lymphocytic Leukemia: meta-analysis

Abstract

Aim: We examined the utility of the rs924607 TT genotype of the centrosomal protein 72 ( CEP72) as a potential biomarker for predilection toward vincristine-induced peripheral neuropathy in children treated for acute lymphoblastic leukemia. Materials & methods: We conducted a random-effects meta-analysis of data from four studies comprising 817 patients. We tested for an association using a recessive model where a one-sided p-value < 0.05 was considered statistically significant. Results and conclusion: We were unable to confirm the association between the rs924607 TT genotype and neurotoxicity (odds ratio: 1.99; p = 0.16; 95% CI: 0.76–5.25) in our global meta-analysis. Analysis of the continuation phase (following induction) studies showed significantly higher odds for neuropathy in CEP72 rs924607 TT homozygotes (odds ratio: 2.28; p = 0.02; 95% CI: 1.16–6.87).

Vincristine-Induced Peripheral Neuropathy in Childhood Acute Lymphoblastic Leukemia: Genetic Variation as a Potential Risk Factor

“… Gutierrez-Camino et al, 2016 ). A meta-analysis for the Spanish subgroup revealed a significant increased risk of VIPN in childhood ALL patients carrying the CEP72 rs924607 TT genotype (OR 2.28; p = 0.02; 95% CI 1.16–6.87) ( Zečkanović et al, 2020 ).…”

Pharmacogenomics of Vincristine-Induced Peripheral Neuropathy in Children with Cancer: A Systematic Review and Meta-Analysis

“…Centrosomes enable correct alignment of chromosomes during mitosis by controlling the position and orientation of the microtubule spindles at the spindle poles [63,64]. A recent meta-analysis on the effect of this SNP in CEP72 on VIPN in children with ALL confirmed this finding across three studies in the continuation phase of treatment [65]. A clinical trial enrolling newly diagnosed children with ALL and lymphomas is randomizing patients with the high risk (TT) genotype between a decreased dosage (1.0 mg/m 2 ) and conventional dosage (1.5 mg/m 2 ) of vincristine during the continuation phase of treatment [66].…”

The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia - a single center experience

“…VCR metabolic pathway is complex. Many transporters and enzymes have important role in the VCR pharmacokinetics and pharmacodynamics and so far, data have not shown a single universal VCR pharmacogenomic marker [29]. This is another example of the failure of predictions that have resulted from GWAS studies.…”

“…This is another example of the failure of predictions that have resulted from GWAS studies. Lack of consistency in neuropathy assessment, grading systems, and the choice of end points make it difficult to interpret results between studies [4,29]. Treatment regiments, including number of VCR doses administered and lengths of VCR treatment, differ between treatment protocols used in different studies [30].…”