Childhood cancer survivors face significant secondary cancer risks, and a new study reveals that genetics play a critical role. Radiation exposure accounts for a ample portion of teh risk, but the contribution of genetic predisposition is often underestimated—even more so than chemotherapy. Researchers found that genetic variants contribute considerably to the risk of subsequent cancers. This groundbreaking research, based on data from the St. Jude LIFE and CCSS studies, the largest survivor cohorts, highlights the importance of considering both primary_keyword and secondary_keyword factors when assessing long-term health outcomes. News Directory 3 can help you find information on further cancer breakthroughs. Discover what’s next for improved screening and survivor strategies.
Genetics Play key Role in Second Cancer Risk for Childhood Cancer Survivors
Updated June 8, 2025
A new study emphasizes the importance of considering genetics when assessing the risk of secondary cancers in childhood cancer survivors. Researchers at St. Jude Children’s Research Hospital found that both genetics and cancer treatment contribute significantly to this risk. Secondary cancers are the primary cause of death for long-term survivors.
The research, published in The Lancet Oncology, analyzed data from the St. Jude Lifetime Cohort Study (St. Jude LIFE) and the childhood Cancer Survivor Study (CCSS). These studies represent the largest survivor cohort in North America.
Yadav Sapkota,PhD,of St.Jude,said the study found that pediatric treatment exposures and genetic predisposition largely contribute to the burden of second cancers in survivors of childhood cancer. he added that while the association between treatment, genetics and second cancer risk was already known, this study is the first to attribute the proportion of their contributions to that risk at the population level.
The study compared data from over 10,000 survivors, including treatment exposures, genetic information, lifestyle factors, and the presence of second cancers. This allowed researchers to evaluate each factor’s contribution.
Greg Armstrong, MD, chair of St. Jude’s Department of Epidemiology and cancer Control, noted that the high-impact discovery was only possible as the CCSS and SJLIFE cohorts have more than 12,000 survivors with genetic sequencing.
Radiation exposure was the most notable factor, accounting for at least 40% of the secondary cancer risk. Modern therapies are already lowering radiation doses or eliminating radiation exposure altogether.
The study also revealed complex relationships between chemotherapy, genetics, and second cancer risk. Chemotherapy contributed between 8% and 35% of the risk, depending on the cancer type. The contribution of genetic predisposition was previously less recognized.
Researchers assessed common genetic variants, known as a polygenic risk score, and rare genetic variants. They found that the polygenic risk score contributed between 5% and 37% of the risk, depending on the cancer type.
Yutaka Yasui, PhD, also of St. Jude, said that polygenic risk scores may provide useful information in conjunction with therapy exposures for estimating the risk of certain types of subsequent cancer among survivors of childhood cancer.
Our findings showed that genetics can be equally or more important than chemotherapy in some second cancers, which is counter to conventional wisdom in the field,” Sapkota said.
Lifestyle factors, such as diet and exercise, contributed less than expected, accounting for only 1% to 6% of the risk. researchers noted that the survivors in the study were primarily in their 20s and 30s,suggesting that lifestyle factors may not have had enough time to manifest their effects.
What’s next
The study suggests that healthcare providers should better account for genetic predisposition when determining second cancer risk in childhood cancer survivors. Those with a strong predisposition could benefit from more frequent cancer screenings. Survivors, armed with knowledge of their individual risk factors, can also advocate for appropriate screening.
