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Research unveils possible mechanisms behind the link between womb cancer risk and BMI. FreshSplash/Getty Images
  • The International Agency for Research on Cancer (IARC) recognizes 13 cancers as linked to obesity, and therefore considers some cases as potentially preventable.
  • One of these types of cancers is endometrial cancer, cases of which have increased by 59% since the early 90s in the United Kingdom.
  • A new study has demonstrated how increased body mass index (BMI) may affect different hormones in a way that could explain its link to endometrial cancer.

Endometrial cancer is the most common cancer affecting the female reproductive tract in high-income countries. In the U.K., one in 36 women are estimated to be diagnosed with endometrial cancer in their lifetime.

Research has indicated that women with a high BMI are more at risk of developing endometrial cancer.

BMI is calculated using a person’s height and weight and is used to determine if a person’s weight is within a healthy range. A BMI score of 20-25 is considered ‘healthy’, a BMI over 25 is considered overweight, over 30 is considered obese, and over 40 is considered severely obese, as accepted by the NHS. BMI is an indirect measure of fat tissue and it is less accurate in some individuals, hence remains controversial.

Dr. Sarah Gray, a general practioner who specializes in women’s health, told Medical News Today in an interview that 20 years ago she worked on developing guidelines at The National Institute for Health and Care Excellence (NICE) for women with heavy periods, which can be a symptom of endometrial cancer. The guidelines concluded that “the chance of getting uterine cancer below the age of 45, was really very remote”.

She explained that as rates of obesity had increased in the population, this had changed:

“I’ve got a colleague who is now occasionally seeing uterine cancer in women in their early 30s,” she said.

Now, a study published in BMC Medicine has quantified the increase in the risk of endometrial cancer in women with a high BMI and has proposed a mechanism for the link.

A team led by researchers from the University of Bristol, with support from Cancer Research U.K., carried out an analysis of genetic samples and health information taken from the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the U.K. Biobank.

Of the 121,885 women largely of European descent (from Australia, Belgium, Germany, Poland, Sweden, the U.K., and the U.S.) included in this study, 12,906 of these women had endometrial cancer.

They found an increase of 5 BMI points was associated with an 88% increase in risk of developing endometrial cancer.

They also discovered that increased testosterone, increased fasting insulin, and decreased sex hormone-binding globulin were associated with an increase in the risk of developing endometrial cancer.

Further analysis by the researchers also found evidence that BMI had an effect on fasting insulin, sex hormone-binding globulin, bioavailable testosterone, and the inflammatory marker C-reactive protein.

The authors hypothesize that increased BMI indicated increased fat tissue, which leads to increased fasting insulin and reduced sex hormone-binding globulin. This, in turn, leads to increased bioavailable testosterone. This testosterone can then be converted into estrogen, which may also increase the risk of endometrial cancer.

Dr. Alpa Patel, senior vice president of population science at the American Cancer Society, explained the link between BMI and endometrial cancer risk wasn’t necessarily a new one.

“We do know that especially in visceral fat that surrounds an organ, [which] is quite metabolically active, [that] is what increases your risk of both insulin resistance and hyperinsulinemia or higher levels of insulin, which can affect endometrial cancer risk,” she told MNT.

Dr. Patel also touched on how menopause and hormonal changes may affect cancer risk.

“After menopause, in fat cells themselves, you have conversions, of androgen (such as testosterone) to estrogen through an enzyme called aromatase. And that [ultimately] increases the conversion to different types of estrogen, and estradiol, which increases your risk of endometrial cancer because it is a hormone-related cancer in women.”
— Dr. Alpa Patel

Dr. Patel said there was a direct link between excess body weight after menopause, owing to the increases in the conversion of androgen to estrogen, which can also increase the risk of endometrial cancer.

“So, it’s not the androgens like testosterone alone. It’s the increased conversion of those to estrogen through aromatase after menopause,” she added.

Dr. James Yarmolinsky, the lead author of the study from the University of Bristol Medical School, explained to MNT how the study could influence clinical practice.

“We try to understand mechanisms. This potentially opens up the possibility of targeting these particular molecules implicated, so mainly insulin and testosterone,” he said.

“[There are] medications like metformin, for example, which we know can increase insulin signaling. [T]hey help in the management of type 2 diabetes, which, in principle, potentially, could be repurposed in some way for endometrial cancer chemoprevention,” he suggested.

Dr. Yarmolinsky said that the findings alone couldn’t say whether this was a viable approach but it was a first step in the right direction.

Dr. Gray, meanwhile, said the study’s findings could prompt women with a high BMI to be more aware of the symptoms of endometrial cancer, so they seek medical help in a timely manner.

“Women who are particularly obese need to be able to monitor their periods. If they go chaotic, erratic, or heavy, then the test is ever so simple. It’s going to be an ultrasound and/or a sample taking,” she said.