Park Joo-Hyun, Hong Jung Yong, Han Kyungdo, Kang Wonseok, Shen Jay J
Department of Family Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea.
Department of Healthcare Administration and Policy, School of Public Health, University of Nevada Las Vegas, Las Vegas, NV 89154, USA.
Cancers (Basel). 2025 Apr 14;17(8):1322. doi: 10.3390/cancers17081322.
: Given the rising incidence of early-onset endometrial cancer diagnosed before the age of 50 years, this study examined whether non-alcoholic fatty liver disease (NAFLD) served as an independent risk factor for early-onset endometrial cancer, irrespective of obesity status. : This nationwide cohort study included 2,311,949 Korean women aged 20-39 years who underwent health screenings from 2009 to 2012. NAFLD severity was classified based on the fatty liver index: none (<30), moderate (30-59), and severe (≥60). Multivariable-adjusted Cox proportional hazards models were applied to estimate adjusted hazard ratios (aHRs) for early-onset endometrial cancer. : During a median follow-up of 7.6 years, 1289 women developed early-onset endometrial cancer. The cumulative incidence of early-onset endometrial cancer was significantly higher in women with NAFLD than in those without (log-rank < 0.001). A dose-dependent association was observed, with increased risk corresponding to greater NAFLD severity (aHR [95% confidence interval (CI)]: moderate NAFLD, 2.38 [1.99-2.85]; severe NAFLD, 5.39 [4.44-6.53]; for trend < 0.01). Compared with non-obese women without NAFLD, the aHRs for early-onset endometrial cancer were 2.53 [2.11-3.05] in non-obese women with NAFLD, 1.66 [1.10-2.52] in obese women without NAFLD, and 4.30 [3.60-5.13] in obese women with NAFLD (synergy index = 1.50, < 0.01). : NAFLD was independently associated with increased risk of early-onset endometrial cancer in both non-obese and obese women. Furthermore, young women with both NAFLD and obesity exhibited a synergistically elevated risk. Early identification and management of NAFLD may help mitigate the rapidly growing burden of early-onset endometrial cancer.
鉴于50岁之前诊断出的早发性子宫内膜癌发病率不断上升，本研究探讨了非酒精性脂肪性肝病（NAFLD）是否为早发性子宫内膜癌的独立危险因素，而不考虑肥胖状况。
这项全国性队列研究纳入了2311949名年龄在20至39岁之间、于2009年至2012年接受健康筛查的韩国女性。NAFLD严重程度根据脂肪肝指数分类：无（<30）、中度（30 - 59）和重度（≥60）。应用多变量调整的Cox比例风险模型来估计早发性子宫内膜癌的调整后风险比（aHRs）。
在中位随访7.6年期间，1289名女性患上早发性子宫内膜癌。NAFLD女性的早发性子宫内膜癌累积发病率显著高于无NAFLD女性（对数秩检验<0.001）。观察到剂量依赖性关联，NAFLD严重程度越高风险越高（aHR[95%置信区间（CI）]：中度NAFLD，2.38[1.99 - 2.85]；重度NAFLD，5.39[4.44 - 6.53]；趋势检验<0.01）。与无NAFLD的非肥胖女性相比，有NAFLD的非肥胖女性早发性子宫内膜癌的aHR为2.53[2.11 - 3.05]，无NAFLD的肥胖女性为1.66[1.10 - 2.52]，有NAFLD的肥胖女性为4.30[3.60 - 5.13]（协同指数 = 1.50，<0.01）。
NAFLD与非肥胖和肥胖女性早发性子宫内膜癌风险增加独立相关。此外，同时患有NAFLD和肥胖的年轻女性风险协同升高。NAFLD的早期识别和管理可能有助于减轻早发性子宫内膜癌迅速增长的负担。
