Rising burden and deepening inequalities: a national study of high BMI-related uterine cancer in the United States using GBD and NHANES data.

OBJECTIVE: Uterine cancer mortality is rising in the U.S. while other cancer deaths decline, posing a major public health challenge. High BMI is the strongest modifiable risk factor, but its full burden and associated inequalities remain poorly characterized. METHODS: Using data from Global Burden of Disease 2023 and National Health and Nutrition Examination Survey (NHANES, 1999-2023), we assessed national and state-level trends in uterine cancer mortality (age-standardized mortality rate [ASMR]) and disability-adjusted life years (age-standardized disability-adjusted life year rate [ASDR]) from 1990-2023. We employed Joinpoint regression, frontier analysis, and AutoRegressive Integrated Moving Average forecasting. Individual-level BMI associations were evaluated using weighted multivariable logistic regression. RESULTS: The ASMR and ASDR for high BMI-related uterine cancer in the U.S. significantly exceeded global averages, with the gap widening. The fastest increase occurred during 2009-2017. Significant geographic disparities were identified; West Virginia and Mississippi were consistent hotspots with high burden and rapid growth. A state's socio-demographic index was negatively correlated with the growth rate (estimated annual percentage change) of ASMR (ρ=-0.709) and ASDR (ρ=-0.726), indicating faster deterioration in socioeconomically disadvantaged regions. NHANES analysis confirmed a significant, dose-response relationship between BMI and uterine cancer risk (adjusted odds ratio per 1-unit BMI increase=1.03, 95% confidence interval=1.01-1.06), which strengthened over time. Subgroup analyses revealed stronger associations in obese individuals, non-Hispanic whites, and women aged ≥50 years. CONCLUSION: High BMI drives the rising and unequal uterine cancer burden in the U.S., underscoring the urgent need for interventions targeting both obesity and health inequities.