Age Specific Risks of Uterine Cancer in Type 2 Diabetes and Associated Comorbidities in Taiwan

SIMPLE SUMMARY: The incidence of uterine cancer is increasing worldwide in recent decades, especially in the young age population. In parallel, a trend of early onset of diabetes mellitus (DM) and obesity was also observed in the young population. Since DM and obesity are known risk factors of uterine cancer, we proposed to investigate the age-specific risks of uterine cancer in subjects with DM and related metabolic comorbidities. In this nationwide population-based study, we found the risk of uterine cancer in DM subjects was significantly higher in the younger age groups, especially in the age group 30–39 years. Obesity, polycystic ovarian syndrome, hyperlipidemia, statin use, and hormone replacement therapy were also significantly associated with uterine cancer in subjects younger than 50 years of age. Therefore, subjects with DM, especially younger women with respective comorbidities, should be recommended to have appropriate uterine cancer screenings for early detection. ABSTRACT: Introduction: The global incidence of uterine cancer has increased substantially in recent decades. We evaluated if the trend of increasing prevalence of diabetes mellitus (DM) and obesity are attributed to the development of uterine cancer. Methods: Using data derived from the National Health Insurance database and Taiwan Cancer Registry, multivariate Cox proportional hazards regression models were adapted to analyze the risk factors of uterine cancer with potential confounding variables. Results: There were a total of 5,104,242 women aged 30–70 years enrolled in the study and 147,772 of them were diagnosed with DM during 2005–2007. In a total of 11 years of follow-up, 14,398 subjects were diagnosed with uterine cancer. An elevated risk of uterine cancer was observed in women with DM of all ages (HR 1.66, 95% CI 1.53–1.81, p < 0.0001). The effect of DM was highest at age 30–39 years (RR 3.05, 95% CI 2.35–3.96, p < 0.0001). In the group of <50 years old, DM patients had at least a twofold higher risk of developing uterine cancer (HR 2.39, 95% CI 2.09–2.74, p < 0.0001). Subjects among all ages diagnosed with polycystic ovary syndrome (PCOS) (HR 2.91, 95% CI 2.47–3.42, p < 0.0001), obesity (HR 2.13, 95% CI 1.88–2.41, p < 0.0001), and those undergoing hormone replacement therapy (HRT) (HR 1.60, 95% CI 1.33–1.93, p < 0.0001) were also positively associated with uterine cancer. Positive associations of hyperlipidemia (HR 1.33, 95% CI 1.22–1.46, p < 0.0001) and statin use (HR 1.27, 95% CI 1.12–1.44, p = 0.0002) on uterine cancer were only observed in subjects <50 years. On the contrary, hyperlipidemia was negatively associated with uterine cancer in subjects ≥50 years (HR 0.91, 95% CI: 0.84–0.98, p = 0.0122). Conclusions: DM is in general the most important risk factor for uterine cancer, especially in premenopausal women. Obesity, PCOS, HPL, statin use, and HRT were also associated with uterine cancer in subjects younger than 50 years. Premenopausal women with DM and respective comorbidities should be aware of the development of uterine cancer.