Diabetes, Obesity, and Endometrial Cancer: A Review

Endometrial cancer is the fourth most diagnosed cancer in U.S. women. Diabetes and obesity are established independent risk factors for EC, but their combined effect is less defined. This review investigates the literature on these comorbidities as risk factors and modifiers of EC. Multiple cohort and case-control investigations have shown an increased relative risk (RR) and odds ratio (OR) when diabetes and obesity coexist. In one prospective cohort, the RR of EC in diabetic women was 1.94 [95% CI, 1.23-3.08], but increased to 6.39 [95% CI, 3.28-12.06] with obesity; with low physical activity added, RR rose to 9.61 [95% CI, 4.66-19.83]. Case-control studies similarly show an OR of 1.4 [95% CI, 0.9-2.4] for diabetes alone, vs. 5.1 [95% CI, 3.0-8.7] with BMI > 30 and diabetes. Mechanistically, both conditions promote a pro-cancerous microenvironment through metabolic and inflammatory pathways. They also worsen treatment outcomes, with greater surgical complications, thromboembolic events (p < 0.01), prolonged hospitalizations 6.2 days versus 4.5 days (p < 0.03), and poorer survival with an elevated cancer-specific mortality (HR = 2.65, 95% CI 1.60-4.40). These findings underscore the urgent need for targeted interventions and translational research on how these comorbidities impact the pathophysiologic processes of EC.