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Leveraging Genetic Insights to Understand Cancer Risks in Childhood Cancer Survivors

TAIPEI, TAIWAN, Mar 28, 2024- Childhood cancer survivors navigate a unique set of health challenges into adulthood. Not only do they grapple with the long-term effects of cancer treatment, but they also bear a heightened risk of developing secondary cancers later in life. Recent studies have shed light on the interplay between genetic factors and treatment history in shaping the landscape of cancer risk among these survivors.

Led by Todd M. Gibson, Ph.D., researchers at the National Cancer Institute (NCI) delved into the complex relationship between inherited genetic variants and cancer predisposition in childhood cancer survivors. Their study, published in Nature Medicine, underscores the potential of genetic insights in tailoring risk assessment and long-term care for this vulnerable population.

Gibson and his team analyzed data from genome-wide association studies (GWAS) to identify common genetic variants associated with various cancers in the general population. They then assessed the impact of these variants on the risk of developing secondary cancers among 11,220 childhood cancer survivors enrolled in two large cohort studies.

The findings revealed a compelling link between polygenic risk scores (PRS) derived from cancer-specific genetic variants and the likelihood of developing subsequent malignancies. Importantly, this association held true for most cancer types studied, including basal cell carcinoma, female breast cancer, thyroid cancer, squamous cell carcinoma, melanoma, and colorectal cancer.

Of particular significance was the observation that the combination of high PRS and past exposure to radiation therapy significantly heightened the risk of certain cancers, surpassing the additive effects of each factor alone. For instance, survivors with elevated PRS and a history of high-dose radiation were markedly more susceptible to basal cell carcinoma, female breast cancer, and thyroid cancer compared to those with lower PRS or less intense radiation exposure.

The implications of these findings are profound. They suggest that genetic profiling could serve as a valuable tool in stratifying cancer risk among childhood cancer survivors, enabling more personalized screening and surveillance strategies. By identifying individuals at the highest risk of specific cancers, healthcare providers can tailor interventions to mitigate these risks and facilitate early detection.

However, the researchers caution that further validation and exploration are needed before integrating PRS into clinical practice. Additional studies involving diverse populations are warranted to ensure the generalizability of these findings. Moreover, evaluating the clinical utility of PRS in guiding follow-up care for childhood cancer survivors is imperative.

In essence, this research represents a significant step forward in our understanding of the genetic underpinnings of cancer risk among childhood cancer survivors. By harnessing genetic insights, healthcare providers can empower survivors to proactively manage their health and minimize the burden of secondary cancers in the years following their initial diagnosis and treatment.


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