Adult survivors of childhood cancer have high rates of obesity, which, in combination with the cardiotoxic effects of specific cancer therapies, places them at high risk for cardiovascular morbidity. Here we show the contribution of genetic risk scores (GRSs) to increase prediction of those survivors of childhood cancer who are at risk for severe obesity (body mass index ≥40 kg m⁻²) as an adult. Among 2,548 individuals of European ancestry from the St. Jude Lifetime Cohort Study who were 5-year survivors of childhood cancer, the GRS was found to be associated with 53-fold-higher odds of severe obesity. Addition of GRSs to risk prediction models based on cancer treatment exposures and lifestyle factors significantly improved model prediction (area under the curve increased from 0.68 to 0.75, resulting in the identification of 4.3-times more high-risk survivors), which was independently validated in 6,064 individuals from the Childhood Cancer Survivor Study. Genetic predictors improve identification of patients who could benefit from heightened surveillance and interventions to mitigate the risk of severe obesity and associated cardio-metabolic complications.

儿童癌症的成年幸存者肥胖率很高，再加上特定癌症治疗的心脏毒性作用，使他们面临心血管发病的高风险。在这里，我们展示了遗传风险评分（GRS）对提高对成年后有严重肥胖风险（体重指数≥40 kg m ^{− 2} ）的儿童癌症幸存者的预测的贡献。 St. Jude 终生队列研究的 2,548 名欧洲血统的儿童癌症幸存者 5 年中，发现 GRS 与严重肥胖的几率高出 53 倍相关。将 GRS 添加到基于癌症治疗暴露和生活方式因素的风险预测模型中，显着改善了模型预测（曲线下面积从 0.68 增加到 0.75，导致识别出的高风险幸存者增加了 4.3 倍），这一结果在来自儿童癌症幸存者研究的 6,064 人。遗传预测因子可以提高对可受益于加强监测和干预措施的患者的识别，从而降低严重肥胖和相关心脏代谢并发症的风险。