New research suggests that lifelong excess body weight is associated with an increased risk of developing endometrial cancer, and testosterone, insulin, and sex hormone binding globulin may play a causal role in this relationship. The research was published in BMC Medicine.1
“Links between obesity and womb cancer are well known, but this is one of the largest studies which has looked into exactly why that is on a molecular level,” lead study author Emma Hazelwood, a PhD student at the University of Bristol in the United Kingdom, said in a statement.2
Hazelwood and colleagues conducted a meta-analysis of 17 genome-wide association studies, which included data from 12,906 patients with endometrial cancer and 108,979 control individuals.
The researchers identified single-nucleotide polymorphisms associated with 14 molecular risk factors for endometrial cancer. The team then used Mendelian randomization (MR) to evaluate the mediating roles of these risk factors in the relationship between body mass index (BMI) and endometrial cancer.
BMI was strongly associated with the risk of developing endometrial cancer, with an odds ratio (OR) of 1.88 per 4.7 kg/m2 increase in BMI (95% CI, 1.69-2.09; P =3.87 x 10-31).
Other significant factors associated with an increased risk of endometrial cancer were total testosterone, bioavailable testosterone, fasting insulin, sex hormone binding globulin, and total serum cholesterol.
Three of these factors appeared to play a mediating role in the relationship between BMI and endometrial cancer risk. These factors were fasting insulin (19% total effect mediated; 95% CI, 5%-34%; P =9.17 x 10-3), bioavailable testosterone (15% mediated; 95% CI, 10%-20%; P =1.43 x 10-8), and sex hormone binding globulin (7% mediated; 95% CI, 1%-12%; P =1.81 x 10-2).
“Our comprehensive MR analysis provides insight into potential causal mechanisms linking BMI with endometrial cancer risk and suggests targeting of insulinemic and hormonal traits as a potential strategy for the prevention of endometrial cancer,” the researchers concluded.
1. Hazelwood E, Sanderson E, Tan VY, et al. Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: A Mendelian randomization analysis. BMC Medicine. 2022;20:125. doi:10.1186/s12916-022-02322-3
2. Excess weight almost doubles risk of womb cancer. News release. Cancer Research UK. Published April 18, 2022. Accessed April 26, 2022. https://www.eurekalert.org/news-releases/949813