Epidemiologic Evidence for the Obesity-Endometrial Cancer Relationship

Abstract

There are convincing epidemiologic evidence that obesity increases endometrial cancer risk and consistent positive associations between body mass index (BMI) and other adiposity parameters and endometrial cancer risk have been observed across different study populations. Indeed, the risk of endometrial cancer is estimated to be 1.54-times higher per 5 kg/m2 increment increase in BMI—an association with BMI that is the strongest that has been observed for any type of cancer. The higher risk of endometrial cancer among overweight and obese women appears to be restricted to those who have not used postmenopausal hormone therapy, suggesting that the modulation of estrogenic activity may be a possible mechanism that underlies the obesity-endometrial cancer link. Further, circulating estrogen levels are positively associated with endometrial cancer risk and partly explain the obesity-endometrial cancer association in mediation models. Another key mechanism that may link obesity with endometrial cancer risk includes hyperinsulinemia as supported by both experimental and observational data. Inflammation and increased exposure to inflammatory cytokines derived from adipose tissue represent additional putative pathways that could contribute to the role of obesity in endometrial cancer development. This review summarizes results from epidemiologic studies on obesity (assessed as BMI, waist circumference and other measures) and endometrial cancer development, highlights mechanisms that may link obesity to endometrial carcinogenesis, and discusses areas of ongoing and future research that could help to develop improved strategies for endometrial cancer prevention.