Childhood Cancer Survivors Have Higher Rate of Aging-Related Mutations Than the General Population

Childhood cancer survivors tended to have a higher rate of aging-related mutations in stem cells — a condition called clonal hematopoiesis — compared to the general population, according to recent research published in the journal Cancer Discovery.

The researchers on the study analyzed blood samples from 2,860 survivors of pediatric cancer and compared them with samples of 324 individuals with no cancer history. Findings showed that clonal hematopoiesis was present in 15% of the childhood cancer survivor group and 8.6% in the non-cancer group.

Notably, a history of treatment with alkylating agents, radiotherapy and bleomycin were all significantly associated with an increased risk of clonal hematopoiesis, as were certain types of cancers: Hodgkin lymphoma, soft tissue sarcoma, germ cell tumors, rhabdomyosarcoma, neuroblastoma, non-Hodgkin lymphoma and acute lymphoblastic leukemia.

“The data are telling us that (clonal hematopoiesis) mutations are important biomarkers that have potential clinical implications for risk of adverse long-term outcomes among the growing population of survivors of childhood cancer,” study co-senior author Leslie L. Robison, a faculty member at St. Jude Children’s Research Hospital in Memphis, said in a press release.

Clonal hematopoiesis is a stem cell-driven process that becomes more common with age. So the researchers also sought to determine if the clonal hematopoiesis was different in those with prior cancer treatment history compared to the general population. To do so, they separated clonal hematopoiesis-related events into two categories: those related to age and those related to cancer treatment.

Findings revealed that certain genes, such as STAT3, were associated with treatment-related clonal hematopoiesis — particularly in survivors of Hodgkin lymphoma. In fact, the presence of STAT3 mutations were present in 17.9% of treatment-related clonal hematopoiesis events, and 6.25% of age-related clonal hematopoiesis.

Upon further study, the researchers found that STAT3 mutations were often highly enriched in T cells that were isolated from the peripheral blood, and were associated with COSMIC SBS25, a mutation signature that has previously been linked with exposure to procarbazine (a chemotherapy agent) in Hodgkin lymphoma cells.

Some cancer centers are starting to steer away from procarbazine use, and the study authors emphasized that these findings offer more of a reason to do so. The researchers also stressed the importance of longer follow-up for childhood cancer survivors.

“We need to follow these patients longitudinally (over time) to understand the clinical implications of having a clone and how the clones evolve and expand over time,” Robison said.

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