Scientists from St. Jude Children’s Research Hospital have identified variants in two genes that may be associated with accelerated aging in childhood cancer survivors. Their research looked at the difference between the survivors’ biologic age and chronologic age. The study, published by Dong et al 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 United States survive their disease; 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 study author Zhaoming Wang, PhD, of the Departments of Epidemiology and Cancer Control and Computational Biology at St. Jude’s. “We previously evaluated nongenetic 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.”
Research Details
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 of survivors’ DNA. Dr. Wang’s group analyzed the link between common genetic variants derived from the whole-genome sequencing data with epigenetic age acceleration in SJLIFE participants. Epigenetic age acceleration is a measure of the difference between biologic and chronologic age for each survivor, and it strongly correlates with the development of age-related diseases.
Dr. 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 approach. In this technique, the researchers compare the DNA variants present in survivors and community controls with different levels of biologic aging. In the 3 billion base pair DNA genome, over 8 million variants were tested, and there were two single-nucleotide polymorphisms that appeared significantly different between individuals with different levels of biologic aging. These single-nucleotide polymorphisms—in combination with other nongenetic risk factors—may allow physicians to identify 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,” Dr. 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.”
Disclosure: The study was funded by grants from the National Institutes of Health, the V Foundation, and ALSAC, the fundraising and awareness organization of St. Jude. For full disclosures of the study authors, visit genomemedicine.biomedcentral.com.
