Joffe Lenat, Mirzaei Sedigheh, Bhatia Shalini, Darji Himani, Ness Kirsten K, Onerup Aron, Ladas Elena J, Im Cindy, Lupo Philip J, Oeffinger Kevin C, Friedman Danielle Novetsky, Howell Rebecca M, Conces Miriam R, Arnold Michael A, Armstrong Gregory T, Neglia Joseph P, Yasui Yutaka, Kadan-Lottick Nina S, Turcotte Lucie M
Northwell, New Hyde Park, New York.
Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
JAMA Oncol. 2025 Jun 5. doi: 10.1001/jamaoncol.2025.1340.
High body mass index (BMI) and low physical activity levels are risk factors for adult-onset cancers. Limited data exist on their relationship with subsequent neoplasms among childhood cancer survivors.
To evaluate associations between time-varying BMI/physical activity and subsequent neoplasm risk among childhood cancer survivors.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort analysis included 5-year childhood cancer survivors diagnosed younger than 21 years of age between 1970 and 1999, enrolled in the Childhood Cancer Survivor Study (CCSS), with follow-up through September 2019 at pediatric tertiary care hospitals in the US and Canada. The data analysis was performed between March 2021 and July 2024.
Self-reported time-varying BMI and maximum reported physical activity (metabolic equivalent of task h/wk [MET-h/wk]) before any subsequent neoplasm development; first assessed at cohort entry and up to 6 times thereafter.
Cumulative incidence by physical activity level and relative rates (RRs) by physical activity and time-varying BMI categories, adjusted for demographic and clinical variables, were estimated for any, subtype (hematologic, solid organ, central nervous system [CNS], skin), and specific (breast, thyroid, colorectal, meningioma) subsequent neoplasms using piecewise exponential models.
Of 25 658 enrolled CCSS participants, 22 716 had BMI data before subsequent neoplasm development and met eligibility criteria for this study (46.3% female; median [range] attained age, 33.7 [5.7-67.3 years]). Among 22 716 survivors, 2554 subsequent neoplasms occurred among 2156 individuals (56.7% female; median [range] age at subsequent neoplasm diagnosis, 37.4 [13.7-63.3] years). Survivors reporting lower physical activity had higher 30-year subsequent neoplasm cumulative incidence: 18.6% (95% CI, 17.0-20.3) for 0 MET-h/wk vs 10.9% (95% CI, 9.9-12.1) for 15-21 MET-h/wk. Obese BMI was associated with increased incidence rates of solid organ (RR, 1.22; 95% CI, 1.01-1.46), CNS (RR, 1.47; 95% CI, 1.12-1.95), and skin (RR, 1.30; 95% CI, 1.13-1.50) subsequent neoplasms. Higher physical activity (15-21 MET-h/wk) demonstrated a protective association for any (RR, 0.61; 95% CI, 0.53-0.71), solid organ (RR, 0.65; 95% CI, 0.52-0.83), CNS (RR, 0.50; 95% CI, 0.35-0.70), and skin (RR, 0.72; 95% CI, 0.60-0.86) subsequent neoplasms. BMI and physical activity were specifically associated with subsequent meningiomas and thyroid carcinomas, but not with breast or colorectal cancers, nor hematologic subsequent neoplasms.
Among childhood cancer survivors in this cohort study, obesity was associated with an increased risk for multiple subsequent neoplasm types, while higher physical activity was associated with reduced subsequent neoplasm risk. Lifestyle interventions should be considered in future subsequent neoplasm prevention research.
高体重指数（BMI）和低身体活动水平是成人期癌症的危险因素。关于它们与儿童癌症幸存者后续肿瘤的关系的数据有限。
评估儿童癌症幸存者中随时间变化的BMI/身体活动与后续肿瘤风险之间的关联。
设计、设置和参与者：这项回顾性队列分析纳入了1970年至1999年间诊断为21岁以下的5年儿童癌症幸存者，他们参加了儿童癌症幸存者研究（CCSS），并在美国和加拿大的儿科三级护理医院随访至2019年9月。数据分析于2021年3月至2024年7月进行。
自我报告的随时间变化的BMI和在任何后续肿瘤发生之前报告的最大身体活动量（代谢当量任务小时/周[MET-h/wk]）；在队列入组时首次评估，此后最多评估6次。
使用分段指数模型估计按身体活动水平的累积发病率以及按身体活动和随时间变化的BMI类别调整人口统计学和临床变量后的相对率（RRs），以评估任何、亚型（血液学、实体器官、中枢神经系统[CNS]、皮肤）和特定（乳腺癌、甲状腺癌、结直肠癌、脑膜瘤）后续肿瘤。
在25658名参加CCSS的参与者中，22716人在后续肿瘤发生之前有BMI数据且符合本研究的纳入标准（46.3%为女性；达到的年龄中位数[范围]为33.7[5.7 - 67.3岁]）。在22716名幸存者中，2156人发生了2554例后续肿瘤（56.7%为女性；后续肿瘤诊断时的年龄中位数[范围]为37.4[13.7 - 63.3]岁）。报告身体活动较低的幸存者3年后续肿瘤累积发病率更高：0 MET-h/wk时为18.6%（95%CI，17.0 - 20.3），而15 - 21 MET-h/wk时为10.9%（95%CI，9.9 - 12.1）。肥胖BMI与实体器官（RR，1.22；95%CI，1.01 - 1.46）、CNS（RR，1.47；95%CI，1.12 - 1.95）和皮肤（RR，1.30；95%CI，1.13 - 1.50）后续肿瘤的发病率增加相关。较高的身体活动（15 - 21 MET-h/wk）对任何（RR，0.61；95%CI，0.53 - 0.71）、实体器官（RR，0.65；95%CI，0.52 - 0.83）、CNS（RR，0.50；95%CI，0.35 - 0.70）和皮肤（RR，0.72；95%CI，0.60 - 0.86）后续肿瘤显示出保护关联。BMI和身体活动与后续脑膜瘤和甲状腺癌特别相关，但与乳腺癌或结直肠癌以及血液学后续肿瘤无关。
在这项队列研究中的儿童癌症幸存者中，肥胖与多种后续肿瘤类型的风险增加相关，而较高的身体活动与后续肿瘤风险降低相关。在未来的后续肿瘤预防研究中应考虑生活方式干预。
