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Researchers find gene responsible for heart damage caused by chemotherapy

September 24, 2015
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(Vancouver – Sept. 24, 2015) – Researchers at the Child & Family Research Institute (CFRI) BC Children’s Hospital and the University of British Columbia (UBC) have found a genetic variation that brings a five times higher risk of heart damage for cancer patients treated with a type of chemotherapy drug called anthracyclines. 

Anthracyclines are a critical, life-saving treatment for leukemia, bone tumours and other cancers in both children and adults. In many patients, the drugs cause permanent heart damage that can lead to heart failure – which can be immediate or develop years after treatment – and may require a heart transplant. Anthracyclines are prescribed to over 900,000 patients each year worldwide. 

The research is published in the September print issue of Nature Genetics. 

The researchers’ previous work identified two genes linked to anthracycline-related heart problems. Their new discovery of a variation in the RARG gene allows for more precise genetic testing to identify patients at risk of these toxic side effects. 

Doctors at BC Children’s Hospital are now leading new research that combines genetic testing with patient clinical information to personalize treatment for children with many common types of cancer.

Quotes:

Dr. Bruce Carleton – study co-lead investigator, CFRI senior scientist, and UBC professor of pediatrics.

  • “Anthracycline cardiotoxicity is a devastating problem. These drugs are responsible in part for dramatically improving the survivability of many cancers, but tragically in some patients they are also responsible for heart failure.  In some cases heart transplants can save patient lives – but heart transplantation is not the best outcome for cancer patients.”

Dr. Colin Ross – study co-lead investigator, CFRI scientist and UBC assistant professor of pediatrics. 

  • “Now that we’ve identified this new gene, it opens the door to administering a rapid predictive test to identify patients at the highest risk of anthracycline cardiotoxicity, before the drug is administered, helping quantify the drug’s benefit and risk in a specific patient. With this new knowledge, we are also working to develop new protective strategies to prevent this toxicity from occurring in the future.” 

Dr. Rod Rassekh – study co-author, pediatric oncologist at BC Children’s Hospital, associate clinician scientist at the Child & Family Research Institute (CFRI), and UBC clinical assistant professor of pediatrics.

  • “The genetic testing provides real-time genetic results that allow us to carefully consider modifying treatment for kids who are at high risk of heart damage. We must weigh the risks of drug toxicity against cure rate and involve families in decision-making to personalize treatment for their child.”

About the study:

There were 456 children who joined the study between February 2005 and April 2011. This included 280 children from cancer units across Canada, 96 children from the Netherlands and 80 non-European ancestry children from Canada and the USA. All of the children had normal heart function before receiving anthracyclines for their cancers. The researchers analyzed the children’s genomes including genes involved in drug biotransformation. This allowed them to identity the RARG gene and its effects on the development of anthracycline-induced heart damage. The genetic analysis was done at the Canadian Pharmacogenomics Network for Drug Safety core facility at the Child & Family Research Institute at BC Children’s Hospital.

All of the children had normal heart function before receiving anthracyclines for their cancers. The researchers analyzed the children’s genomes including genes involved in drug biotransformation. This allowed them to identity the RARG gene and its effects on the development of anthracycline-induced heart damage. The genetic analysis was done at the Canadian Pharmacogenomics Network for Drug Safety core facility at the Child & Family Research Institute at BC Children’s Hospital.

This research was supported by the Canadian Institutes of Health Research (CIHR), the US National Institutes of Health, a Stanford Comprehensive Cancer Center Translational Research Grant, the Child & Family Research Institute, BC Children’s Hospital Foundation, Bertram Hoffmeister Postdoctoral Fellowship Award, Michael Smith Foundation for Health Research, Canada Foundation for Innovation, Genome British Columbia, the Provincial Health Services Authority, the University of British Columbia, the Canadian Gene Cure Foundation, the C17 Research Network, and the Childhood Cancer Foundation – Candlelighters Canada.

The Child & Family Research Institute conducts discovery, translational and clinical research to benefit the health of children and their families. CFRI is supported by BC Children's Hospital Foundation and works in close partnership with BC Children’s Hospital, the Provincial Health Services Authority and its agencies, and the University of British Columbia. For more information, visit www.bcchr.ca

BC Children’s Hospital, an agency of the Provincial Health Services Authority, provides expert care for the province’s most seriously ill or injured children, including newborns and adolescents. It is an academic health centre affiliated with the University of British Columbia, Simon Fraser University, and the Child & Family Research Institute. Sunny Hill Health Centre for Children is the provincial facility that offers specialized child development and rehabilitation services to children and youth. For more information, visit www.bcchildrens.ca.

The University of British Columbia (UBC) is one of North America’s largest public research and teaching institutions, and is consistently ranked among the world’s 40 best universities. Surrounded by the beauty of the Canadian West, it is a place that inspires bold, new ways of thinking that have helped make it a national leader in areas as diverse as community service learning, sustainability and research commercialization. UBC offers more than 58,000 students a range of innovative programs and attracts $519 million per year in research funding from government, non-profit organizations and industry through over 8,000 projects and grants. For more information, visit www.ubc.ca.

Read more:

Aminkeng F, Bhavsar AP, Visscher H, Rassekh SR, Li Y, Lee JW, Brunham LR, Caron HN, van Dalen EC, Kremer LC, van der Pal HJ, Amstutz U, Rieder MJ, Bernstein D, Carleton BC, Hayden MR, Ross CJ; Canadian Pharmacogenomics Network for Drug Safety Consortium. A coding variant in RARG confers susceptibility to anthracycline-induced cardiotoxicity in childhood cancer in Nature Genetics, September 2015. doi: 10.1038/ng.3374

Contact:

Jennifer Killam, CFRI Communications
Tel: 604.875.2401  jkillam@bcchr.ca  www.bcchr.ca