Chronologically young, biologically old: DNA linked to cancer survivors premature aging
Date:
March 22, 2022
Source:
St. Jude Children's Research Hospital
Summary:
Scientists have identified variants in two genes that are associated
with accelerated aging in childhood cancer survivors.
FULL STORY ========================================================================== Scientists from St. Jude Children's Research Hospital have identified
variants in two genes that are associated with accelerated aging in
childhood cancer survivors. Their research looked at the difference
between their biological age and chronological age. The study, published
today in Genome Medicine, is the first to identify genetic risk factors
for accelerated aging in pediatric cancer survivors.
========================================================================== Today a majority of children with cancer in the U.S. survive. However,
some survivors develop diseases that typically occur in older adults. It
is not totally clear why some patients are more susceptible to developing age-related conditions than others.
"This is one of a series of studies my lab has undertaken to investigate
aging biomarkers in childhood cancer survivors," said corresponding
author Zhaoming Wang, Ph.D., of the Departments of Epidemiology and
Cancer Control and Computational Biology. "We previously evaluated
non-genetic risk factors including cancer treatments, health behaviors,
and chronic health conditions that contribute to age acceleration. This
study focuses on the underlying genetic factors among these patients."
St. Jude follows over 6,000 childhood cancer survivors enrolled in the
St. Jude Lifetime Cohort Study (SJLIFE). As part of SJLIFE, scientists
have characterized genetic variations by conducting whole-genome
sequencing (WGS) of survivors' DNA. Wang's group analyzed the link
between common genetic variants derived from the WGS data with epigenetic
age acceleration (EAA) in SJLIFE participants. EAA is a measure of the difference between "biological" and chronological age for each survivor,
and it strongly correlates with the development of age-related diseases.
Finding the Premature Aging Needle in a Genetic Haystack Wang's group
found variants in two genomic regions associated with the development
of accelerated aging. One variant was in the SELP gene and the other in
the HLA region. These genes are both involved in age-related diseases.
For example, SELP is upregulated in Alzheimer's disease.
The scientists found the variants by employing an agnostic Genome-Wide Association Study (GWAS) approach. In this technique, the researchers
compare the DNA variants present in survivors and community controls with different levels of biological aging (i.e., EAA). In the 3 billion base
pair DNA genome, over 8 million variants were tested, and there were
two single nucleotide polymorphisms (SNPs) that appeared significantly different between individuals with different levels of biological
aging. These SNPs in combination with other non-genetic risk factors may
allow physicians in the future to identify the survivors at higher risk
of accelerated aging before they develop premature aging symptoms.
"Our work can help determine subgroups at the highest risk for accelerated aging among childhood cancer survivors," Wang said. "The findings can
also identify potential drug targets for future invention studies. For
example, the protein produced by the SELP gene, p-selectin, already has
an inhibitor used in other diseases." All data analyzed in the paper
is publicly available for other researchers in the St. Jude Cloud, which provides data and analysis resources to the global research community.
The study's co-first authors are Qian Dong and Nan Song, both of
St. Jude. The study's other authors are Cheng Chen, of Shanghai Jiaotong University; Zhenghong Li, Xiaojun Sun, John Easton, Heather Mulder, Emily Plyler, Geoffrey Neale, Emily Walker, Qian Li, Xiaotu Ma, Xiang Chen,
I-Chan Huang, Yutaka Yasui, Kirsten K. Ness, Jinghui Zhang, Melissa
M. Hudson, and Leslie L. Robison of St. Jude. The study was funded by
grants (CA021765 and CA195547) from the National Institutes of Health,
the V Foundation and ALSAC, the fundraising and awareness organization
of St. Jude.
========================================================================== Story Source: Materials provided by
St._Jude_Children's_Research_Hospital. Note: Content may be edited for
style and length.
========================================================================== Journal Reference:
1. Qian Dong, Nan Song, Na Qin, Cheng Chen, Zhenghong Li, Xiaojun
Sun, John
Easton, Heather Mulder, Emily Plyler, Geoffrey Neale, Emily Walker,
Qian Li, Xiaotu Ma, Xiang Chen, I-Chan Huang, Yutaka Yasui, Kirsten
K. Ness, Jinghui Zhang, Melissa M. Hudson, Leslie L. Robison,
Zhaoming Wang.
Genome-wide association studies identify novel genetic
loci for epigenetic age acceleration among survivors
of childhood cancer. Genome Medicine, 2022; 14 (1) DOI:
10.1186/s13073-022-01038-6 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220322122541.htm
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