ESPE Yearbook of Paediatric Endocrinology

Brief summary: This study evaluated the ability of genetic risk scores to predict severe obesity in adult survivors of childhood cancer. Data from 2548 survivors of European ancestry from the St. Jude Lifetime Cohort Study was analyzed and findings were validated in 6064 survivors from the Childhood Cancer Survivor Study. Survivors with higher genetic risk scores had significantly higher odds of severe obesity. Adding genetic risk scores to prediction models that included cancer treatment exposures and lifestyle factors improved prediction accuracy.

Overweight, obesity, and increased risk for diabetes mellitus and cardiovascular disease are common, but often overlooked and undertreated, sequelae of cancer treatment in children, adolescents, and adults (1,2). Cardiovascular morbidity is a major burden for this growing patient population, resulting in impaired quality of life and excess mortality (3,4).

This study of adult survivors of childhood cancer provides important clinical and scientific insights into the risk factors and prediction of severe obesity in this population. The findings highlight the considerably high prevalence of obesity among survivors, emphasizing the need for early identification and targeted interventions. Factors contributing to obesity include treatment exposures (cranial radiation, total body irradiation, corticosteroids), lifestyle behaviours (reduced physical activity, low energy expenditure), and genetic susceptibility (5). Importantly, the study introduces the concept of genetic risk scores as a valuable tool to improve the prediction of severe obesity in childhood cancer survivors. The inclusion of genetic risk scores based on common and rare genetic variants associated with obesity significantly improved the prediction models, resulting in improved identification of high-risk survivors. Incorporating genetic risk scores into risk prediction models has therefore the potential to improve patient management and facilitate targeted interventions, ultimately leading to better long-term health outcomes for this vulnerable population.

References: 1. Mostoufi-Moab S, Seidel K, Leisenring WM, Armstrong GT, Oeffinger KC, Stovall M, Meacham LR, Green DM, Weathers R, Ginsberg JP, Robison LL, Sklar CA. Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study. J Clin Oncol 2016; 34:3240–3247. 2. Kapoor A, Prakash V, Sekhar M, Greenfield DM, Hatton M, Lean ME, Sharma P, Han TS. Monitoring risk factors of cardiovascular disease in cancer survivors. Clin Med (Lond) 2017; 17:293–297. 3. Armstrong GT, Liu Q, Yasui Y, Neglia JP, Leisenring W, Robison LL, Mertens AC. Late mortality among 5-year survivors of childhood cancer: a summary from the Childhood Cancer Survivor Study. J Clin Oncol 2009; 27:2328–2338. 4. Mertens AC, Liu Q, Neglia JP, Wasilewski K, Leisenring W, Armstrong GT, Robison LL, Yasui Y. Cause-specific late mortality among 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 2008; 100:1368–1379. 5. Gebauer J, Higham C, Langer T, Denzer C, Brabant G. Long-term endocrine and metabolic consequences of cancer treatment: a systematic review. Endocr Rev. 2019 Jun 1;40(3):711–767.