SNP Linked to Vincristine-Related Neuropathy in ALL

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SNP Linked to Vincristine-Related Neuropathy in ALL
SNP Linked to Vincristine-Related Neuropathy in ALL

(HealthDay News) -- A single-nucleotide polymorphism (SNP) in the promoter region of the CEP72 gene, which encodes a centrosomal protein involved in microtubule formation, correlates with risk and severity of vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia (ALL), according to a study published in the Feb. 24 issue of the Journal of the American Medical Association.

Barthelemy Diouf, Pharm.D., Ph.D., from the St. Jude Children's Research Hospital in Memphis, Tenn., and colleagues examined genetic germline variants associated with the occurrence or severity of vincristine-induced peripheral neuropathy in children with ALL. SNP analysis and vincristine-induced peripheral neuropathy were assessed in 321 patients: 222 enrolled in the St. Jude Children's Research Hospital protocol Total XIIIB and 99 enrolled in the Children's Oncology Group (COG).

The researchers found that during continuation therapy, grade 2 to 4 vincristine-induced neuropathy occurred in 28.8 percent of patients in the St. Jude cohort and in 22.2 percent in the COG cohort. A SNP in the promoter region of CEP72 was significantly associated with vincristine neuropathy. Among patients with high-risk CEP72 genotype (TT at rs924607), 56 percent developed at least one episode of grade 2 to 4 neuropathy, compared with 21.4 percent in patients with CEP72 CC or CT genotypes. Neuropathy severity was higher for patients with TT versus CT or CC genotypes.

"If replicated in additional populations, this finding may provide a basis for safer dosing of this widely prescribed anticancer agent," the authors write.

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