Gene Variant May Up Peripheral Neuropathy Risk with Chemo Drug
The first genetic variation linked to increased risk and severity of peripheral neuropathy following treatment with a common chemotherapy drug has been identified, according to scientists at St. Jude Children's Research Hospital. Findings from the study are published in the Journal of American Medical Association.
The study evaluated 321 children and adolescents who were treated with 36–39 doses of vincristine for acute lymphoblastic leukemia (ALL). A total of 50 patients (16%) inherited two copies of the high-risk CEP72 gene variant. After screening for almost one million common inherited gene variations, 60.8% of patients who inherited two copies of CEP72 developed peripheral neuropathy. Vincristine-related peripheral neuropathy was diagnosed in 23.4% of patients who inherited at least one of the more common versions of CEP72. Also, those with two copies of the CEP72 gene variant had double the risk of developing serious, disabling, or life-threatening peripheral neuropathy vs. other patients.
The CEP72 gene variant was also linked to an increased sensitivity to vincristine, which may suggest the possibility of lowering vincristine doses in these patients. Plans are underway to study this option in newly diagnosed pediatric patients with ALL later this year.
Researchers concluded that the high-risk CEP72 gene variant was associated with an increased risk of peripheral neuropathy despite other risk factors (eg, race, vincristine dose). Specifically, the high-risk version of the gene was less commonly seen in African-Americans.
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