BMI is Strongly Associated with Uterine Cancer Risk
Yes, body mass index (BMI) is one of the strongest established risk factors for uterine cancer, with a clear dose-response relationship showing that higher BMI levels progressively increase cancer risk. 1, 2
Magnitude of Risk by BMI Category
The association between BMI and uterine cancer risk follows a linear, dose-dependent pattern:
- Overweight (BMI 25-30): Associated with a 1.32-fold increased risk (32% increase) compared to normal weight women 1, 2
- Mild obesity (BMI 27.5-29.5): Associated with a 43% increased incidence 2
- Obesity (BMI ≥30): Associated with a 2.54 to 2.73-fold increased risk (154-173% increase) 1, 2
- Severe obesity (BMI ≥35-40): Associated with a 4.7-fold increased risk, representing the highest magnitude of association 2, 3
Each 1-unit increase in BMI is independently associated with an 11% increase in uterine cancer risk, demonstrating that even modest weight gain significantly raises cancer risk. 4 For endometrioid adenocarcinomas specifically (the most common histologic subtype), very obese women (BMI ≥40) have an 11.1-fold increased risk compared to lean women. 5
Strength and Quality of Evidence
The evidence linking BMI to uterine cancer is considered "convincing" by major cancer organizations, representing the highest level of epidemiologic certainty. 1 This conclusion is supported by:
- Multiple meta-analyses showing consistent dose-response relationships 1
- A meta-analysis of metabolic syndrome components identifying obesity as having the greatest relative risk (2.21) among all metabolic factors 1
- Large cohort studies demonstrating linear relationships between BMI and cancer probability 4
The European Society for Medical Oncology (ESMO) and American College of Obstetricians and Gynecologists (ACOG) both recognize obesity as among the strongest modifiable risk factors for endometrial cancer. 1, 2
Clinical Context and Trends
The incidence of endometrial cancer is increasing by 0.7-0.82% annually in the United States, with mortality rising 1.1-1.9% per year, directly linked to rising obesity rates. 2 This makes BMI management increasingly important for cancer prevention at the population level.
Impact on Prognosis After Diagnosis
Beyond increasing cancer risk, obesity also worsens outcomes after diagnosis:
- 20% higher all-cause mortality among women with obesity at diagnosis 1, 2
- Roughly twofold increased endometrial cancer-specific mortality 2, 3
- However, obesity paradoxically correlates with better prognostic tumor features (low grade, endometrioid histology, early stage) 1
Important Caveats
Obesity often acts as a confounding factor with other risk conditions. For example:
- Polycystic ovarian syndrome (PCOS) shows a 2.79-2.89-fold increased risk, but when adjusted for BMI, this drops to 2.2, indicating obesity independently contributes 1, 6
- Type 2 diabetes has been questioned as an independent risk factor once obesity is accounted for 1
The relationship is linear across the entire BMI spectrum, meaning there is no "safe" threshold of overweight—risk increases continuously with each BMI unit gained. 4
Mechanistic Understanding
The biological mechanisms linking BMI to uterine cancer include:
- Postmenopausal women: Adipose tissue converts androstenedione to estrone, creating unopposed estrogen stimulation without progesterone 2
- Premenopausal women: Obesity causes insulin resistance, elevated androgens, anovulation, and chronic progesterone deficiency 2
- Additional pathways include chronic inflammation, adipokines, and hyperinsulinemia 1, 2