St. Jude Children's Research Hospital, Memphis, TN, USA.
School of Public Health, University of Alberta, Edmonton, AB, Canada.
Nat Med. 2022 Aug;28(8):1590-1598. doi: 10.1038/s41591-022-01902-3. Epub 2022 Jul 25.
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) 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.
成年癌症患儿幸存者中肥胖率较高，加之特定癌症治疗的心脏毒性作用，使他们患心血管疾病的风险很高。在这里，我们展示了遗传风险评分（GRS）对增加预测那些成年后患严重肥胖（体重指数≥40kg/m2）风险的儿童癌症幸存者的贡献。在来自圣裘德终身队列研究的 2548 名欧洲血统的儿童癌症 5 年幸存者中，发现 GRS 与严重肥胖的几率增加 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，显著提高了模型预测的准确性（曲线下面积从 0.68 增加到 0.75，从而识别出 4.3 倍的高危幸存者），这在来自儿童癌症幸存者研究的 6064 名个体中得到了独立验证。遗传预测因子可提高对可能受益于加强监测和干预以减轻严重肥胖及相关代谢并发症风险的患者的识别。
