Abstract
Addition of genetic risk score to prediction models improves obesity risk prediction in adult survivors of childhood cancer.
Major Finding: Addition of genetic risk score to prediction models improves obesity risk prediction in adult survivors of childhood cancer.
Concept: Genetic risk score was associated with 53-fold higher odds of severe obesity and allowed identification of 4.3-times more high-risk survivors.
Impact: These results identify those who would benefit from enhanced surveillance and interventions to reduce obesity risk.
Adult survivors of pediatric cancers have an increased risk of chronic health conditions related to toxicities of cancer treatment. Risk for potentiating these chronic health conditions is also exacerbated by the enhancement of modifiable risk factors like obesity in this patient population, further contributing to premature mortality. Previous studies have suggested a genetic susceptibility to obesity, with genome-wide association studies indicating rare and common variants associated with body mass index (BMI), leading to the generation of a genetic risk score (GRS) connected with developing severe obesity. However, a need for a prediction model for obesity among adult survivors of childhood cancer remains; therefore, Sapkota and colleagues sought to characterize severe obesity in long-term survivors of pediatric cancers as well as to develop and validate prediction models to identify those at high risk of developing severe obesity. Among survivors of European ancestry from the St. Jude Lifetime (SJLIFE) cohort, male sex, irradiation to brain, chest, pelvis, abdomen, and hypothalamus–pituitary axis, exposure to glucocorticoids, smoking, and physical activity were demonstrated as significant predictors of at least one of the BMI categories, including overweight, obesity, and severe obesity. GRSrare, defined as the GRS based on 14 rare/low-frequency protein-altering variants associated with BMI in the general population, indicated higher odds of being overweight or obese in both the SJLIFE training cohort as well as the Childhood Cancer Survivor Study (CCSS) validation cohort. Likewise, GRScommon exhibited higher odds of overweight, obesity, and severe obesity, resulting in individuals in the top decile being 53-times more likely to develop severe obesity. Inclusion of the GRSs in prediction models identified 4.3-times more high-risk survivors within the SJLIFE cohort of European ancestry as compared to the clinical model alone, with similar results observed in CCSS survivors of European ancestry. Overall, this study developed and validated a prediction model of obesity risk in survivors of childhood cancers, which can be used to guide surveillance and intervention measures in high-risk populations to mitigate chronic health conditions and improve quality of life.
Note:Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.
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