St. Jude Children's Research Hospital investigators have discovered inherited genetic variations that are associated with rapid hearing loss in young cancer patients treated with the drug cisplatin. The research appears in the current online issue of the scientific journal Nature Genetics.
Cisplatin is one of the most widely used anti-cancer drugs and is a mainstay of treatment for children and adults with many types of brain and other solid tumors. But in some patients the drug causes debilitating side effects, including severe hearing loss.
Researchers checked the DNA of 238 young brain tumor patients for more than 1.7 million common genetic variations. Variations in a gene named ACYP2 were associated with as much as a four-fold greater risk of cisplatin-related hearing loss. The screening is among the first to survey the genetic landscape for clues to help explain why the risk of cisplatin-related hearing loss varies so widely among patients.
The association between the high-risk ACYP2 variants and cisplatin-related hearing loss was confirmed in a separate group of 68 young brain tumor patients. The link was independent of other risk factors for cisplatin-related hearing loss, including patient age and radiation therapy.
Twenty-four of the 306 patients in this study had at least one copy of the high-risk ACYP2 variant. All 24 patients had measurable hearing loss that occurred as early as weeks after beginning cisplatin therapy. Overall, however, the ACYP2 variant explained a relatively small proportion of hearing damage. Just 12.4 percent of the 194 patients in this study with cisplatin-related hearing loss carried the ACYP2 variant.
Learn more at the St, Jude Children’s Research Hospital website
