A national study led by the University of Alabama at Birmingham (UAB) is helping explain why some childhood cancer survivors develop new cancers years after their original treatment. The research, published in the Journal of Clinical Oncology, found that inherited genetic changes can greatly increase the chance of developing a second cancer later in life.
Childhood cancer survivors already face a higher risk of new cancers because of the radiation and chemotherapy used to treat their first disease. This study shows that risk is even higher for survivors who carry certain genetic mutations that affect how the body protects itself from cancer.
The research team studied more than 1,100 childhood cancer survivors from across the country. They compared two groups: 499 survivors who developed a second cancer and 625 survivors who did not. By analyzing DNA samples, researchers looked for harmful mutations in genes that normally help prevent cancer.
Researchers found that survivors with one of these mutations were more than four times as likely to develop a second cancer as those without a mutation. Some treatments increased risk even more. Radiation raised the odds of a second cancer more than 16 times, and a type of chemotherapy called platinum-based treatment doubled the risk. Survivors with a TP53 mutation, a gene that plays a major role in protecting the body from cancer, had an especially high risk.
The most common second cancers found in the study were skin, thyroid, brain, breast and bone cancers, as well as soft tissue sarcomas. Many of these cancers appeared more than 10 years after the first cancer, showing the importance of long-term follow-up care.
Smita Bhatia, M.D., MPH, distinguished professor in the Division of Pediatric Hematology and Oncology, led the UAB team for this national study
“Childhood cancer survivors are at increased risk of new cancers that are directly related to the radiation and chemotherapy used to treat the primary cancer,” said Bhatia.
She explained that carrying a harmful genetic mutation increases that risk even more and that these patients benefit from closer follow-up and screening to find new cancers early.
“We have developed a risk calculator that allows healthcare providers to identify which childhood cancer survivors would benefit from genetic testing that would identify survivors who are at the highest risk of developing second cancers,” Bhatia explained.
To help physicians know who needs closer monitoring, the team created a risk calculator that uses simple information such as a survivor’s age at diagnosis, cancer type, and past treatments. When genetic test results were added, the tool became even more accurate.
Using this tool, researchers found that about one in five survivors were at low risk, while nearly four in five were at moderate to high risk for developing a second cancer. Most survivors who carried a harmful mutation were in the higher risk group.
The findings offer a new way to personalize care for childhood cancer survivors by helping doctors decide who may need genetic testing and closer screening. The goal is to catch second cancers earlier and improve long-term health for survivors.