U of A study identifies genetic variant contributing to hearing loss in children treated with cancer drug cisplatin

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A recent study from the University of Alberta identified a genetic variant that contributes to the risk of hearing loss in children treated with the cancer drug cisplatin.

Amit Bhavsar, Assistant Professor in the Department of Medical Microbiology and Immunology, participated in an international effort to find a genetic contribution to children who develop hearing loss after being treated with cisplatin. According to Bhavsar, the team examined nearly a million genomic sequences and found one that caught their attention.

“There was that really intriguing [genetic variant] called TCRG1L, which is a transcriptional regulator, ”Bhavsar said. “We don’t know much about it yet, but the key point is that it had never been associated with cisplatin-induced hearing loss before. It was certainly a new genetic direction to take.

Bhavsar’s team found an association between the TCERG1L variant and hearing loss in children treated with cisplatin. According to Bhavsar, this association is important for two main reasons.

Since TCRG1L is a transcriptional regulator protein, this would suggest that TCERG1L controls the expression of many other genes. Bhavsar described his team as intrigued by the genes over which TCERG1L has control.

“It is likely that one of these genes [TCERG1L] Controls actually play a very important role in cisplatin-induced hearing loss, ”he explained. “We would be really interested in trying to better understand the family of genes controlled by TCERG1L.”

Second, this study could help prevent cisplatin-induced hearing loss. Knowing that children with the genetic variant TCERG1L have an approximately three-fold increased risk of developing cisplatin-induced hearing loss may prompt clinicians to test children for TCERG1L before treating them with cisplatin.

“What this allows you to do, given the current advancement in genomics, is that you can actually do a painless test… that would let a clinician know if that child they want to treat [with cisplatin] to the [TCERG1L] variant or not ” Bhavsar noted. “If they have this variant, it might help them make a more informed choice about how they want to treat this patient.”

Looking ahead, Bhavsar described his team as being focused on preventing cisplatin-induced hearing loss by treating cancer with co-therapies.

“Cisplatin is a very important chemotherapy drug… it’s really good at killing cancer, but you just want to use it safely,” Bhavsar said. “We aim to develop co-therapies that you can administer at the same time as cisplatin that would specifically protect children against the development of hearing loss, so that they can still benefit from the drug and the great uses of cisplatin – which is the anticancer effect – but they would not be at risk of developing hearing loss. “


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