Obesity, demographic, and lifestyle risk factor patterns associated with endometrial cancer diagnosis and survival: insights from the Women's Health Initiative

Background: Obesity, the major risk factor for endometrial cancer, has varying prevalence geographically. We aimed to examine patterns in obesity, demographic characteristics, lifestyle risk factors and histopathologic features among women with and without endometrial cancer and to evaluate their association with survival outcomes. Methods: We utilized data from the Women’s Health Initiative cohort study to analyze 93,676 postmenopausal women with a uterus enrolled between 1993 and 1998, followed through 2021. Demographic and lifestyle characteristics were compared between women with and without endometrial cancer using absolute standardized mean differences. Histologic subtype and stage at diagnosis were stratified by race and geographic region. Multivariable Cox proportional hazards models assessed associations between demographic and lifestyle factors and survival. Kaplan-Meier curves and log-rank tests compared survival by region. Results: Our cohort included 92,040 participants without and 1826 participants with incident endometrial cancer over a mean 16.7 (±7.36) years of follow-up. Women with endometrial cancer were more likely to be obese (BMI (body mass index) ≥30), non-Hispanic White, and have hypertension and diabetes. Obesity conferred a higher risk of endometrial cancer, but its effect was not modified by race. Histologic subtype and stage at diagnosis varied by race and region, with women in the South having a higher prevalence of aggressive histologies and advanced-stage cancers. Survival did not differ significantly by region (log-rank p = 0.187) and White vs. Black race did not modify this association (p = 0.857). Conclusions: These findings contribute to our understanding of endometrial cancer epidemiology and highlight the importance of considering racial disparities and histologic subtypes when studying the disease. While survival outcomes did not differ significantly by geographic region, notable disparities in tumor characteristics highlight the importance of a uniform focus on obesity prevention. Equitable access to prevention, early detection and treatment strategies can help inform health policy at the national level.