Obesity and Endometrial Cancer- what are the risks?

In the gynaecological oncology session, Faustino Perez-Lopez discussed the link between obesity, insulin resistance and endometrial cancer.

Endometrial cancer (EC) is the most frequent female genital cancer in developed countries, accounting for around 6% of all cancers in women. Although there is no routine screening test for EC, prevalence of the condition has increased in early years. The majority of women are diagnosed at an early stage so overall survival can be as high as 90%.

The mechanisms of endometrial carcinogenesis remains unclear, but it is thought genetic factors, epigenetic factors, genital microbioma, steroid hormones, obesity and exercise could all be involved. Excessive weight is associated with increased cancer risk and mortality. Data from Reeves et al. 2007 has shown that obesity is more strongly associated with development of endometrial cancers than any other form. The effect of excessive weight was also found to be long term, lasting from adulthood until caner has been diagnosed. Literature has also shown that physical activity can help combat the increased risk. A control study by John et al 2010 showed that the most active cohort (top third of women) were 56% less likely to develop EC compared to the least active cohort (bottom third of women). However additional data has highlighted that the additional benefits of physical activity are different according to BMI. The inverse relation with physical activity is limited to women who are overweight or obese but does not have any benefit in women of a healthy weight.  The WHI carried out an observational study in 36, 794 women to see if intended weight loss could reduce EC risk. Data showed that weight loss of more than 10 pounds in postmenopausal women can significantly reduce risk of EC. However comparing women who had a stable body weight with women who gained at least 5% of their body weight during the study, the latter were significantly more likely to develop EC.

Dougan et al 2015 showed that excessive weight and obesity during childhood and adolescence was also linked to EC risk. A BMI of 23 or higher at age 18 was associated with significantly higher risk of developing EC compared to those with a lower BMI.  Aaarestup et al 2017 showed that obesity in girls as young as 6-14 can increase EC risk. Having a higher adjusted BMI score of one unit higher than average significantly increased risk of developing EC later in life, highlighting the risk obesity at a young age can have.

Penez-Lopez et al 2017 looked at what kind of obesity-related change may be associated with EC risk and found that fasting insulin levels were higher. Obese people are exposed to changes in glucose metabolism and higher levels of insulin. Back in 2015 the same group looked at insulin resistance and EC risk and found that women with EC cancer at time of diagnosis had a significantly higher amount of insulin compared to the women who don’t have cancer. This led to the conclusion that during carcinogenesis women have higher levels of insulin. Data from a WHI study looking at the association between diabetes, diabetes treatment and endometrial cancer survival time also shows that EC survival time is reduced in women with type II diabetes highlighting another risk factor link.

It is clear that the expanding rates of obesity across the world pose a huge risk for development of endometrial cancer. Literature shows that there is a well-defined relationship between EC and obesity, hyperinsulinemia, insulin resistance and type II diabetes. We have also learnt that the negative effect of excess weight on EC risk begins many years before diagnosis of malignancies as obesity is linked to changes in the body. Physical activity and weight loss can help reduce risk in obese women, so it is imperative patients are educated on lifestyle changes.

Check back later to hear an update on ovarian cancer!