Excessive weight can significantly contribute to a woman’s chances of developing womb cancer. A new paper places the increased risk per extra body mass index (BMI) unit at twice that of previous estimates.

New research at the University of Bristol reports that every 5 extra BMI units in lifelong weight can increase a woman’s risk of developing endometrial (womb) cancer by a whopping 88%. Those 5 BMIs are the difference between someone who is overweight and someone in the obese category; for a 5-foot 5-inch adult woman, an increase of 5 BMI is equivalent to 28 pounds of weight.

The results of this paper point to a much larger effect of increased lifelong body weight on endometrial cancer. This is likely due to the study focusing on the effects of lifelong increased weight rather than looking at only a snapshot in the lives of women like previous research, the team explains.

A weighty issue

“We show that lifelong elevated BMI causes a larger increased risk than that reported in previous conventional observational studies. We found strong evidence for a mediating role of fasting insulin, bioavailable testosterone, and sex hormone-binding globulin (SHBG) in the effect of BMI on endometrial cancer risk. These results suggest targeting of insulin-related and hormonal traits as a potential strategy for the prevention of endometrial cancer,” the paper reads.

Endometrial cancer is known to be closely linked with overweight and obesity. It is the most common gynecological cancer in high-income countries; around one-third of these cases are estimated to be caused by excess weight. This makes it the second-highest cause of preventable cancer in many parts of the developed world behind smoking.

In a bid to better understand the biochemical link between excessive weight and endometrial cancer, the study analyzed genetic samples from around 120,000 women in Australia, Belgium, Germany, Poland, Sweden, the UK, and the U.S.; out of these, roughly 13,000 had womb cancer. From this wealth of genetic data, the researchers looked for the markers of 14 different traits previously linked with obesity and endometrial cancer.

The paper had three objectives. First, the team looked to validate or invalidate previous findings of the existence of a causal relationship between higher BMIs and increased endometrial cancer risk — their findings supported the existence of this link. Secondly, they looked at previously-reported-on factors and how they influence the risk of developing womb cancer. Third, they quantified how much of the overall added risk of developing endometrial cancer was mediated by each of the factors confirmed in the previous step.

All in all, the team reports that three hormones (fasting insulin, testosterone, and SHBG) seem to be particularly linked with an increased risk of an individual being diagnosed with endometrial cancer. Knowing how obesity works to increase the risk of cancer, such as through the activity of these two hormones, the team explains, we can design better treatments or medicine to better reduce the incidence of this disease. The authors point to drugs like metformin which is used in treating diabetes and can reduce the levels of fasting insulin in patients; such treatments could also affect the risk of cancer emergence, although this has not yet been confirmed.

“This study is an interesting first step into how genetic analyses could be used to uncover exactly how obesity causes cancer, and what can be done to tackle it,” says Emma Hazelwood from the University of Bristol, lead author of the paper.

“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. We look forward to further research exploring how we can now use this information to help reduce the risk of cancer in people struggling with obesity.”

“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.”

Overall, the authors conclude based on the findings that the targeting of insulin-related and hormonal traits is a promising “potential strategy for the prevention of endometrial cancer” that should be investigated further.

The paper “Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: a Mendelian randomization analysis” has been published in the journal BMC Medicine.