Uncovering Genetic Predictors of Cancer Risk
A recent study led by researchers at the National Cancer Institute (NCI) has unveiled common inherited genetic factors that not only predict cancer risk in the general population but also elevate the risk of new cancers among childhood cancer survivors. Published in Nature Medicine on March 7, 2024, the findings suggest that genetics may play a significant role in the development of subsequent cancers in survivors of childhood cancer, offering potential implications for screening and long-term follow-up care.
Assessing the Combined Effect of Genetic Variants and Radiation Treatment
Childhood cancer survivors face an increased risk of developing new cancers later in life due to the adverse effects of cancer treatment or rare inherited genetic factors. In this study, researchers evaluated the combined effect of common genetic variants and a history of radiation treatment. They found that the resulting elevated cancer risk surpassed the individual associations for treatment and genetic factors alone, indicating a synergistic effect between the two.
Implications for Clinical Practice and Future Research
The study assessed the contribution of common inherited genetic variants to subsequent cancer risk in childhood cancer survivors by analyzing data from genome-wide association studies (GWAS) conducted in large healthy populations. Polygenic risk scores derived from GWAS in the general population were associated with an increased risk of several cancers among childhood cancer survivors, including basal cell carcinoma, female breast cancer, thyroid cancer, squamous cell carcinoma, melanoma, and colorectal cancer.
Moreover, the researchers found that the risk associated with higher radiation exposure and higher polygenic risk scores was greater than expected, suggesting a synergistic effect between genetic predisposition and treatment history. These findings highlight the potential for incorporating genetics into long-term follow-up care for childhood cancer survivors to better assess their risk of subsequent cancers.
However, the study acknowledges limitations, such as the predominantly European ancestry of the populations included in the analysis, warranting further research in diverse populations. While polygenic risk scores are not yet used routinely in clinical practice, they may one day inform screening approaches and clinical decisions. Dr. Todd M. Gibson, lead investigator of NCI’s Division of Cancer Epidemiology and Genetics, emphasized that while these results suggest a potential role for polygenic risk scores in improving guidelines for long-term follow-up, additional research is needed before they can alter existing clinical guidelines.
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