Can DNA be linked to premature aging in cancer survivors?

In this interview, we talk to Dr. Zhaoming Wang about his latest research looking at accelerated aging in childhood cancer survivors and the genetics behind it.

Please, could you introduce yourself and tell us what inspired your recent research?

I am an associate faculty member at St. Jude Children’s Research Hospital, with a primary appointment with the Department of Epidemiology and Cancer Control and a secondary appointment with the Department of Computational Biology. My research on the biomarkers of aging was originally inspired by my colleague, Dr. Keri Ness, who was one of the first to report on the phenomenon of accelerated aging among childhood cancer survivors.

Over the past two years, we have collaborated and published our research demonstrating that biomarkers of aging including leukocyte telomere length (https://aacrjournals.org/clincancerres/article/26/10/2362/82443/Shortened-Leukocyte-Telomere-Length- Ass Associates) and epigenetic age (https://academic.oup.com/jnci/article-abstract/113/5/597/5911122?redirectedFrom=fulltext&login=false) are implicated in acceleration of lifespan. This latest post is the third edition along my focused research on aging.

Although the majority of children in the United States survive cancer, some children can be left with diseases that are typically seen in older adults, and why this occurs is still not fully understood. why is that?

On average, chronic age-related health conditions occur much earlier among survivors than in the general non-cancer population. For example, a 35-year-old survivor may be similar to a 50-year-old non-cancer person in terms of cardiovascular disease risk. However, not all survivors showed the same level of accelerated aging and therefore risk.

We use a biomarker of aging (eg, epigenetic age) to objectively measure the biological age of each survivor and attempt to show that biological aging may explain the difference from one survivor to another in terms of age-related chronic disease.

Image Credit: Justinboat.29 / Shutterstock.com

I have previously evaluated non-genetic risk factors for this accelerated aging. What did you discover from this previous research and why did your team choose to focus on basic genetics this time around?

Our previous research has shown that previous exposures to cancer treatment and health behaviors can influence accelerated aging. These are non-genetic factors and can be used to identify survivors with accelerated aging. For example, a survivor had previously been treated with chest radiation or had adopted an unhealthy lifestyle.

From the literature, we know that biological aging is determined in part by inherited genes. Therefore, we conducted this research to look for genetic factors. In the future, we will be able to use both genetic and non-genetic factors to improve accuracy in identifying survivors with accelerated aging.

In your most recent research, you investigated accelerated aging in pediatric cancer survivors. Can you describe how you did your most recent research and what you discovered?

We took advantage of pre-existing whole-genome sequencing data and used a genome-wide association study (GWAS) approach to search for genetic variations that are closely associated with acceleration of epigenetic lifespan.

We identified two genetic markers of statistical significance, one specific to the SELP gene encoding P-selectin, and one specific to the HLA region encoding genes important for immune function.

In your research, you used data from childhood cancer survivors enrolled in the St. Jude Lifelong Cohort Study (SJLIFE). How important are data sets like these to advancing our understanding of disease and disease?

It is critical to have a resource such as the study of St. .

What are the effects of this accelerated chronological age on these child cancer survivors?

Accelerated aging will lead to the early onset of chronic age-related health conditions and premature death among child cancer survivors.

Saint Jude Cloud: A pediatric genomic data source for the scientific community

Do you think your research can be used to help us identify survivors at high risk of accelerated aging before any symptoms appear? What are the advantages of this not only for healthcare professionals but for patients themselves as well?

yes I do. However, we must extend our research from a single time point to multiple time points (ie measuring epigenetic age and chronic health conditions longitudinally) to provide evidence supporting temporal association. This will eventually lead to precision preventive medicine for healthcare professionals to discuss and implement intervention strategies with patients to slow down the aging process and thus prevent aging-related diseases.

The results of your recent study are publicly available to other researchers at St Jude Cloud? Why did you decide to make your results publicly available? What are the advantages of this in accelerating research in the future?

The data we generated and used in this study is available to the scientific community, so other colleagues in the same field will have access to the data to develop new methods and conduct their own analysis.

It was St. Jude Cloud is an excellent platform for sharing our data, which is not only easily accessible but also ensures that the privacy of our patients is adequately protected.

The ongoing COVID-19 pandemic has highlighted the importance of collaboration in research. How important is collaboration in this research?

This project was started and completed during the pandemic. Most of the people involved had to work remotely. It’s really quite a challenge, but we accomplished it by working virtually together. Research like this requires different expertise, and we have put together a multidisciplinary team including an epidemiologist, a computational biologist and a biostatistician.

What are the next steps for your research?

We plan to conduct further observational studies to examine whether biomarkers of aging can predict healthy span and age among childhood cancer survivors. We also plan to design intervention trials targeting biomarkers of aging.

I predict that this may eventually lead to a paradigm shift in survival and care research: focusing on aging and prolonging health rather than stressing a specific chronic disease.

About Dr. Zhaoming Wang

I currently serve as co-chair of the Genetics and Genomics Working Group for the Cancer Control and Survival Program within the Cancer Center at St. Jude Children’s Research Hospital. My research has focused on three interrelated but progressive areas: 1) the genetic epidemiology of cancers (primary and later). 2) Discovering late-effects biomarkers for pediatric cancer survivors, and 3) Omics-based precision preventive medicine.Dr. Wang

I established myself as an expert in cancer germline genetics during my tenure as the Head of the Bioinformatics Group in the Department of Cancer Epidemiology and Genetics at the National Cancer Institute. One of my most influential contributions to the field of cancer epidemiology and genetics has been the OncoArray design of Genetic Associations and Mechanisms at the Oncology Consortium in 2013, which led to a series of major publications around 2017.

Having joined St. Jude in 2015, I have expanded into biomarker research of aging on pediatric cancer survivors who suffer from accelerated aging and suffer from a high burden of treatment and chronic diseases associated with aging. In 2018, she led the pioneering publication on genetic susceptibility to second cancer in the Journal of Clinical Oncology and followed up with a second major paper on single- and polygenic risk of subsequent breast cancer in clinical cancer research. Since 2007 I have been the author of over 190 publications with over 30,000 citations.

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