Association of CEP72 rs924607 Genetic Variant with Vincristine-Induced Peripheral Neuropathy in Children with Acute Lymphoblastic Leukemia

Abstract

Abstract Objective To investigate the association between the CEP72 rs924607 genetic variant and vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL). Methods Children between the ages of 1 and 18 with ALL were treated with Chinese Children's Cancer Group (CCCG)-ALL2015 or CCCG-ALL2020 from January 2018 to December 2022 at the Hospital of Guizhou Medical University, and VIPN was assessed and recorded using the criteria outlined in the US National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE), 5th edition. Chi-square or Fisher’s tests were used for comparison between groups, and P < 0.05 was considered statistically significant. Results 1) A total of 74 children were included in this study, among whom the C allele frequency was 68.9% and the T allele frequency was 68.9%. 2) In total, 43 patients had at least one episode of grade 2–4 VIPN (58.1%). Among those with the high-risk CEP72 genotype (TT at rs924607), 10 of 11 patients (90.9%) developed VIPN, and 33 of 63 patients had the CEP72 CT + CC genotype (52.4%). The incidence of VIPN in the TT genotypes was higher than the CC + CT genotypes, and there were statistically significant differences in the incidence of VIPN between the TT groups and CT + CC (P < 0.05) groups. 3) Among 43 patients with VIPN, 17 (39.5%) were grade 3 and above, 26 (60.5%) were grade 2, 9 of 18 patients (50%) with the CC genotype had severe VIPN (grade 3 and above), 4 of 15 patients (26.7%) had the CT genotype, and 4 of 10 patients (40%) had the TT genotype. There were no significant differences in the severity of VIPN (P > 0.05). 4) Relationship between the polymorphism of the CEP72rs924607 gene and the type of VIPN: Among all 83 cases of VIPN, 35 cases of autonomic nervous symptoms (42.2%), 40 cases of peripheral nerve injury (48.2%), and 8 cases of cranial nerve injury (9.6%) were reported. There were no significant differences among the three genotypes in VIPN occurrence (P > 0.05). 5) The treatment methods for VIPN focused on observation, use of neurotrophic drugs, analgesics, enemas, and other treatments. Clinical symptoms disappeared 2.6 ± 1.9 days after these treatments, and no case of death or residual peripheral neuropathic injury was reported. Conclusions The CEP72 CC genotype accounted for the highest proportion of children with ALL, followed by CT and then TT. There was a high incidence of VIPN in the T allele. Furthermore, peripheral nerve injury had the highest incidence. The prognosis of VIPN was generally good.