A chemotherapy drug may cause hearing loss in some childhood cancer patients depending on their genetic makeup, researchers in B.C. have found.

Cisplatin, a lifesaving anti-cancer drug used to treat more than one million patients worldwide each year, is often given to children with brain, bone or liver cancer. The drug is also used in many adult cancers, including ovarian, lung, bladder, head and neck.

'In the future, the physician may decide an alternate chemotherapy or alternate dose or method of administration may be more appropriate for a patient at high risk of severe deafness.'— Dr. Colin Ross

The commonly used chemotherapy agent causes side-effects including serious hearing loss in up to 50 per cent of adults receiving high doses and up to 61 per cent of children, according to the study in Sunday's online issue of the journal Nature Genetics.

In children, even mild losses of high-frequency hearing considerably increase a child's risk of learning difficulties and social-emotional problems.

In the study, geneticist Dr. Michael Hayden, director of the Centre for Molecular Medicine and Therapeutics at Vancouver's Child & Family Research Institute, and his colleagues analyzed 220 genes involved in drug metabolism before finding two genetic variants linked to serious hearing loss in children taking cisplatin.

In the short term, the findings will help increase awareness of the problem, said Dr. Colin Ross, the study's lead author.

Identifying genetic variants that contribute to cisplatin-induced hearing loss, such as through a blood or saliva test, is the first step to finding a way to predict which children are at greatest risk, the study's authors concluded.

"This information would help the physician, patient, and family to decide what is the most appropriate course of treatment," Ross said in an email. "In the future, the physician may decide an alternate chemotherapy or alternate dose or method of administration may be more appropriate for a patient at high risk of severe deafness."

Surveillance network underpins study

Other researchers are also working on new medications to prevent cisplatin hearing loss, and genetic testing could identify patients that should receive this protective therapy, he added.

The researchers looked at 54 children receiving cisplatin chemotherapy at BC Children's Hospital. Of this group, 33 children, or 61 per cent, suffered hearing loss that required hearing aids or cochlear implants after the chemotherapy.

Among these children, variants in two genes — called thiopurine methyltransferase or TPMT and catechol-O-methyltransferase gene or COMT — were significantly linked with cisplatin-induced hearing loss.

The findings were confirmed in a second group of 112 children recruited through a national surveillance network for adverse drug reactions at children's hospitals across Canada.

Studies are ongoing to see whether the results also apply to adult patients.

A similar research project is looking at why up to 2,000 Canadian babies per year are at risk of morphine overdose based on their genetic profile when their mothers take narcotic pain relief during childbirth.