Radiation, chemotherapy—or your DNA? A groundbreaking study reveals what really determines the risk of getting cancer a second time.
Key Points at a Glance
- Second cancers are the leading cause of death in childhood cancer survivors.
- New data from over 12,000 survivors shows genetics can rival or exceed chemotherapy in risk contribution.
- Radiation exposure is the strongest known risk factor, responsible for over 40% of second cancers.
- Polygenic risk scores may help personalize cancer screening and prevention in survivors.
Childhood cancer may be treatable, but the story doesn’t end at remission. For tens of thousands of survivors, a shadow looms: the risk of developing cancer again. Scientists at St. Jude Children’s Research Hospital have now identified the most important drivers behind these “second cancers,” and their findings may upend the way survivors are monitored for the rest of their lives.
The large-scale study, published in The Lancet Oncology, draws from two of the most robust survivor databases in existence: the St. Jude Lifetime Cohort (St. Jude LIFE) and the Childhood Cancer Survivor Study (CCSS). Together, these cohorts allowed researchers to analyze the medical and genetic records of more than 12,000 survivors, offering unprecedented insights into what causes cancer to return.
“We’ve always known treatment plays a role, but now we’ve quantified how much it matters—and how much genetics matters too,” said lead researcher Dr. Yadav Sapkota. The headline: radiation therapy, often a crucial part of childhood cancer treatment, is still the top culprit, accounting for 40% or more of the second cancer risk.
However, genetic predisposition isn’t far behind. Using polygenic risk scores—essentially a risk fingerprint based on a person’s DNA—the researchers found that a person’s genes could account for up to 37% of second cancer risk. “That’s more than we expected,” noted Dr. Yutaka Yasui, a co-author on the paper. “In some cases, genetics mattered even more than chemotherapy.”
Surprisingly, lifestyle factors such as diet, exercise, or smoking contributed far less—just 1% to 6%. But this may be a function of age: most survivors in the study were in their 20s or 30s, too young for lifestyle choices to fully manifest their long-term effects. Nevertheless, doctors caution that lifestyle still plays a critical role in preventing other health problems.
This research isn’t just academic—it’s a roadmap for better care. With polygenic risk scores becoming more refined, clinicians might soon use them to personalize follow-up plans. Survivors with a high genetic risk, for example, could receive more frequent and targeted screenings, catching new cancers earlier, when they’re more treatable.
“This work changes the way we think about survivorship,” said Dr. Greg Armstrong. “We can’t just look at what happened during treatment. We have to consider each survivor’s genetic blueprint.”
For survivors and their families, the implications are enormous. This research opens the door to more informed healthcare decisions, better screening strategies, and hopefully—longer, healthier lives. As the fight against cancer continues, the true victory will come not just in survival, but in freedom from fear of its return.
Source: St. Jude Children’s Research Hospital
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