High-risk pair – drug and DNA variant increase heart disease risk in cancer survivors

St. Jude LIFE provides answers

To find the variants most associated with later cardiac problems, researchers compared genetic variants from 1,870 survivors who are part of those enrolled in St. Jude LIFE. St. Jude LIFE is a long-running study tracking the health of five-year survivors who were treated for childhood cancer at St. Jude. The study aims to reduce treatment side effects later in life in childhood cancer survivors. The researchers were able to “rediscover” several known variants associated with cardiac dysfunction, verifying that their approach worked.

In the same analysis, the group found a new variant near the gene KCNK17 associated with cardiac dysfunction. The researchers repeated the analysis in 301 St. Jude LIFE survivors of African descent and confirmed the discovery in this population.

“The whole genome sequencing data was key to finding this variant,” said co-senior author Yutaka Yasui, Ph.D., St. Jude Department of Epidemiology and Cancer Control. “Whole genome sequencing data of over 4,500 survivors that we have in St. Jude LIFE are an exceptional resource for scientific research. We use this precious genomic data in combination with treatment and health outcome data collected through clinical assessment from survivors as adults to identify risk of major late effects of childhood treatment, including cardiomyopathy.”

Validating results

Sometimes genetic findings only apply to the sample of patients used in the study. The scientists wanted to see if their finding could be replicated in an unrelated cohort. So, they ran their analysis with 4,020 survivors of European ancestry enrolled in the CCSS. This cohort includes childhood cancer survivors at least five years post-therapy who were treated at one of 31 participating institutions in the US and Canada. The researchers were able to find the same variant associated with cardiac dysfunction in this population too, validating their results.

The data used to discover the variant in the St. Jude LIFE cohort is freely available to other scientists on the St. Jude Cloud.

Authors and funding

The other co-senior authors is Gregory Armstrong of St. Jude. The other authors from St. Jude are Matthew J Ehrhardt, Na Qin, Zhaoming Wang, Kyla Shelton, Ying Shao, Emily Plyler, Heather L Mulder, John Easton, Robert Michael, Carmen Wilson, Chunliang Li, Jun Yang, Jinghui Zhang, Daniel Mulrooney, Melissa Hudson and Leslie Robison. Additional authors are Qi Liu and Weiyu Qiu, University of Alberta; Paul Burridge, Northwestern University; Xuexia Wang, University of North Texas; John Jefferies, The University of Tennessee Heath Science Center; Eric J Chow, Fred Hutchinson Cancer Research Center; Kevin Oeffinger, Duke University; Lindsay Morton, National Cancer Institute; and Smita Bhatia, University of Alabama at Birmingham.

The study was supported by grants from the National Cancer Institute (CA21765, R01CA261898 and R01CA216354) and ALSAC, the fundraising and awareness organization of St. Jude.

Read the full text of the Journal of the National Cancer Institute article:

A novel locus on 6p21.2 for cancer treatment-induced cardiac dysfunction among childhood cancer survivors

Journal of the National Cancer Institute, published June 13, 2022

St. Jude Children’s Research Hospital

St. Jude Children’s Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 60 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. To learn more, visit stjude.org or follow St. Jude on social media at @stjuderesearch.

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