Genetic Predisposition Significantly Impacts second Cancer Risk in Childhood Cancer Survivors: A New Understanding for Personalized Care
Childhood cancer survival rates have dramatically improved, leading to a growing population of survivors facing the long-term challenge of secondary cancers. For decades, treatment exposures – especially radiation – have been the primary focus when assessing this risk. However, groundbreaking research published recently reveals a far more nuanced picture, highlighting the substantial and ofen greater role of genetic predisposition in determining a survivor’s likelihood of developing a second cancer. This shift in understanding promises to revolutionize surveillance strategies and empower survivors to proactively manage their health.
Beyond Treatment: Unpacking the Contributors to Second Cancer Risk
The study, a collaborative effort involving researchers from St. Jude Children’s Research Hospital, the University of Alberta, and other leading institutions, meticulously analyzed data from the St. Jude LIFE and Childhood Cancer Survivor Study (CCSS).Researchers investigated the contributions of three key factors: radiation exposure, chemotherapy, and genetics, alongside lifestyle influences.
The findings confirm the established link between radiation and increased risk,but importantly,demonstrate that modern treatment protocols – already reducing radiation doses or eliminating them altogether – are effectively mitigating this risk. This reinforces the ongoing progress in minimizing treatment-related late effects.
Though, the most striking revelation centers on the impact of genetics. While chemotherapy contributed to 8-35% of subsequent cancer risk depending on the initial cancer type, genetic predisposition, assessed through both common and rare genetic variants (using a polygenic risk score), accounted for a comparable 5-37% of the risk. In some cases,genetic factors were equally or more crucial than chemotherapy.
“Our findings showed that genetics can be equally or more critically important than chemotherapy in some second cancers, which is counter to conventional wisdom in the field,” explains Dr. Sapkota, a lead researcher on the study.The Promise of Polygenic Risk Scores in Personalized Surveillance
The study leveraged polygenic risk scores – a tool increasingly used in personalized medicine – to assess an individual’s inherited susceptibility to cancer. While thes scores currently lack the precision needed for widespread clinical request in the general population, the research demonstrates their potential value specifically within the childhood cancer survivor population.
“Polygenic risk scores are developed for all kinds of diseases for personalized medicine,but generally with precision below what is required for clinical utility in the general population,” notes Dr. Yutaka Yasui, co-author and expert in epidemiology and cancer control. “Among survivors of childhood cancer and for estimating their risk of certain types of subsequent cancer, however, they may provide useful data in conjunction with therapy exposures.”
Interestingly,lifestyle factors – diet and exercise – appeared to contribute a relatively small percentage of risk (1-6%) in this cohort. Researchers attribute this to the young age of the study participants (20s and 30s), suggesting that the long-term effects of lifestyle choices may become more apparent later in life. Despite this, the importance of healthy lifestyle choices for overall wellbeing remains paramount, particularly in relation to other late effects of treatment like cardiac health.
A Paradigm Shift in Survivorship Care
This research necessitates a basic shift in how we approach long-term care for childhood cancer survivors. Historically, surveillance strategies have heavily emphasized monitoring for late effects directly linked to treatment. Now, a more extensive approach is required, integrating genetic risk assessment into the equation.
“Historically, we have paid attention to survivors’ treatment exposures when determining second cancer risk,” Dr. Sapkota emphasizes. “Our study suggests that we need to better account for genetic predisposition in this population.”
The implications are significant. Survivors identified as having a high genetic predisposition could benefit from more frequent and intensive cancer screenings, allowing for earlier detection and more effective treatment of any secondary cancers that may develop. Furthermore, armed with a deeper understanding of their individual risk profile - encompassing treatment history, genetic factors, and lifestyle – survivors can engage in more informed discussions with their healthcare providers and advocate for personalized surveillance plans.
Looking Ahead: Extending Lives Through Proactive Prevention
Second cancers remain the leading cause of mortality among childhood cancer survivors. This study provides a critical step towards reducing that burden. By quantifying the contributions of treatment, genetics, and lifestyle, researchers have pinpointed key areas for intervention.
“Now that we have quantified the contributions of treatment, genetics and lifestyle to the risk of secondary disease, we have a better understanding of where to focus efforts to prevent, detect and treat these cancers, and hopefully extend these survivors’ lives,” concludes dr. sapkota.This research represents a significant advancement in our understanding of long-term survivorship, paving the way for more personalized, proactive, and ultimately, life-saving care for the growing population of childhood cancer survivors.
Study Funding: This research was supported by grants from the National Cancer Institute (R01HL173881, R01CA2163
