Genetic links between childhood cancer and accelerated epigenetic aging identified.
Childhood cancer is relatively rare, affecting just one in 6,500 children each year. In recent decades, the overall survival rate for children with cancer has increased from 10 percent to 85 percent, due to early diagnosis and marked advancements in treatment. However, findings from a new study suggest that some survivors of childhood cancer are genetically susceptible to experiencing accelerated epigenetic aging.
Epigenetic age acceleration is a phenomenon that occurs when a person’s epigenetic age exceeds their chronological age. Acceleration may be either intrinsic or extrinsic. Intrinsic aging is largely driven by internal physiological factors such as normal metabolism and genetics, whereas extrinsic aging is associated with lifestyle and environmental exposures, such as diet, tobacco use, ultraviolet radiation, and mental illness.
The investigators performed a genome-wide association study, a type of observational study that associates specific genetic variations with particular diseases, using multiple epigenetic aging clocks. Their assessment was based on blood-derived DNA from approximately 2,400 childhood cancer survivors and 500 people who had never had cancer.
They identified single nucleotide polymorphisms, or variants, in two areas of the survivors' DNA – the ¬¬SELP gene and the HLA region – that drive accelerated aging and are associated with age-related disease. The SELP gene encodes for a protein called P-selectin, a cell adhesion molecule that plays roles in atherosclerosis and peripheral artery disease. Its activity is increased in the setting of Alzheimer’s disease. The HLA, or human leukocyte antigen, region is an area on chromosome six that plays important roles in immunity. Mutations in the HLA region, which can occur following exposure to genotoxic drugs (such as chemotherapy) are associated with increased risk for autoimmune disorders, such as type 1 diabetes and celiac disease.
These findings suggest that genetic variants increase the risk of accelerated epigenetic aging among childhood cancer survivors and underscore the importance of identifying children at risk. Learn about epigenetic aging acceleration in this clip featuring Dr. Steve Horvath.
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