Endometrial cancer is the most common gynecological cancer. The most common cause is elevated body mass index (BMI). However, the molecular mechanisms underpinning this association remain unclear.
A new study by the University of Bristol evaluated the causal role of 14 molecular risk factors in endometrial cancer risk. Scientists found that every five extra BMI units double the a woman’s risk of womb (endometrial) cancer.
This is higher than most previous studies have suggested and reflects lifelong weight status rather than a snapshot in time like most other studies. Five BMI units are the difference between the overweight and obese categories, or of a 5’5 adult woman being two stones heavier.
The study involves genetic samples from around 120,000 women from Australia, Belgium, Germany, Poland, Sweden, the UK, and the USA. Thirteen thousand among them had womb cancer.
Scientists observed markers of 14 traits- linking obesity and womb cancer. They uncovered two hormones – fasting insulin and testosterone – which increased the risk of being diagnosed with womb cancer.
By determining how obesity increases the risk of cancer, such as through hormones, scientists in the future could use drugs to reduce or increase the level of these hormones in people already at a higher risk of cancer. For example, drugs like metformin used in diabetes treatment can reduce hormones, and research suggests this drug also affects cancer risk, though further study is ongoing.
Emma Hazelwood, lead author of the paper from Bristol Medical School, said: “This study is an interesting first step into how genetic analyses could uncover exactly how obesity causes cancer, and what can be done to tackle it. Links between obesity and womb cancer are well-known, but this is one of the largest studies that has looked into why that is on a molecular level. We look forward to furthering research exploring how we can now use this information to help reduce the risk of cancer in people struggling with obesity.”
Dr. Julie Sharp, head of health information at Cancer Research UK, said: “Cancer Research UK has been leading the way in uncovering links between obesity and cancer for years. Studies like this bolster the fact that being overweight or obese is the second biggest cause of cancer in the UK and can help us start to pinpoint why. This will play a pivotal role in uncovering how to prevent and treat cancer in the future.”
“More research is needed to investigate exactly which treatments and drugs could be used to manage cancer risk among people struggling with obesity. We already know that being overweight or obese increases your risk of developing 13 different types of cancer. To reduce your cancer risk, it’s important to maintain a healthy weight by eating a balanced diet and staying active.”
- Hazelwood, E., Sanderson, E., Tan, V.Y. et al. Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: a Mendelian randomization analysis. BMC Med 20, 125 (2022). DOI: 10.1186/s12916-022-02322-3