title: Association between diabetes, diabetes treatment and risk of developing endometrial cancer.
abstract: BACKGROUND
  A growing body of evidence suggests that diabetes is a risk factor for endometrial cancer incidence. However, most of these studies used case-control study designs and did not adjust for obesity, an established risk factor for endometrial cancer. In addition, few epidemiological studies have examined the association between diabetes treatment and endometrial cancer risk. The objective of this study was to assess the relationships among diabetes, diabetes treatment and endometrial cancer risk in postmenopausal women participating in the Women's Health Initiative (WHI).
  
  
  METHODS
  A total of 88 107 postmenopausal women aged 50-79 years who were free of cancer and had no hysterectomy at baseline were followed until date of endometrial cancer diagnosis, death, hysterectomy or loss to follow-up, whichever came first. Endometrial cancers were confirmed by central medical record and pathology report review. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% confidence interval (CI)) for diagnosis of diabetes and metformin treatment as risk factors for endometrial cancer.
  
  
  RESULTS
  Over a mean of 11 years of follow-up, 1241 endometrial cancers developed. In the primary analysis that focused on prevalent diabetes at enrolment, compared with women without diabetes, women with self-reported diabetes, and the subset of women with treated diabetes, had significantly higher risk of endometrial cancer without adjusting for BMI (HR=1.44, 95% CI: 1.13-1.85 for diabetes, HR=1.57, 95% CI: 1.19-2.07 for treated diabetes). However after adjusting for BMI, the associations between diabetes, diabetes treatment, diabetes duration and the risk of endometrial cancer became non-significant. Elevated risk was noted when considering combining diabetes diagnosed at baseline and during follow-up as time-dependent exposure (HR=1.31, 95% CI: 1.08-1.59) even after adjusting for BMI. No significant association was observed between metformin use and endometrial cancer risk.
  
  
  CONCLUSIONS
  Our results suggest that the relationship observed in previous research between diabetes and endometrial cancer incidence may be largely confounded by body weight, although some modest independent elevated risk remains.
authors: Department of Epidemiology and Biostatistics, School of Public Health Indiana University Bloomington, 1025 E., 7th Street, Bloomington, IN, 47405, USA.
authors: J
authors: J
authors: Luo
authors: School of Public Health, University of Washington, Seattle, WA, USA.
authors: S
authors: S
authors: Beresford
authors: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: C
authors: C
authors: Chen
authors: Los Angeles BioMedical Research Institute at Harbor-University of California, Torrance Memorial Medical Center, Torrance, CA, USA.
authors: R
authors: R
authors: Chlebowski
authors: Department of Epidemiology, School of Medicine, University of California, Davis, CA, USA.
authors: L
authors: L
authors: Garcia
authors: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors: L
authors: L
authors: Kuller
authors: Department of Biostatistics, School of Public Health, West Virginia University, Morgantown, WV, USA.
authors: M
authors: M
authors: Regier
authors: Department of Social and Preventive Medicine, University at Buffalo, Buffalo, NY, USA.
authors: J
authors: J
authors: Wactawski-Wende
authors: HealthPartners Institute for Education and Research, Minneapolis, MN, USA.
authors: K L
authors: KL
authors: Margolis
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000209:etiology*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D015999:Multivariate Analysis; D017698:Postmenopause; D016016:Proportional Hazards Models; D012307:Risk Factors