Gene Variation and Nerve Disorder Linked to Cancer Drug
Scientists at St. Jude Children's Research Hospital have pinpointed the first genetic variation that is equated with increased risk and severity of peripheral neuropathy, following treatment with a widely used chemotherapy drug.
Findings from the study are published in the Journal of American Medical Association.
Description of the Initial Study
Vincristine is a precscription drug that treats leukemia and many other types of cancer, usually in combination with other medicine. Childhood acute lymphoblastic leukemia (also called ALL or acute lymphocytic leukemia) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated immediately.
A total of fifty patients (16%) inherited two copies of the high-risk CEP72 gene variant. The CEP72 gene encodes a protein that is essential for microtubule formation, and also increased the sensitivity of cancer cells to vincristine.
After screening for almost one million common inherited gene variations, 60.8% of patients who inherited two copies of CEP72 eventually developed peripheral neuropathy. Peripheral neuropathy, a result of damage to your peripheral nerves, often causes weakness, numbness and pain, usually in your hands and feet. It can also affect other areas of your body.
Vincristine-related peripheral neuropathy was diagnosed in 23.4% of patients who inherited at least one of the more common variations of CEP72. Also, those with two copies of the CEP72 gene variant doubles the risk of developing serious, debilitating, or life-threatening peripheral neuropathy vs. other patients.
Final Results of the Study
Like what was stated previously, the CEP72 gene variant was linked to an increased sensitivity to vincristine, which may suggest the possibility of lowering vincristine doses in these patients. Plans are underway to further research and investigate this option in newly diagnosed pediatric patients with ALL sometime later this year.
Researchers deduced 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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