Obesity and uterine (endometrial) cancer

Obesity and excess weight, an increasingly serious problem of our age, are known to accompany many cancers. Nevertheless, the fact that obesity is among the most important risk factors for endometrial cancer (womb = uterus) unfortunately receives insufficient attention, and awareness remains very low.

Compared with other cancer types, uterine cancer has a particularly strong association with obesity

This relationship adds powerful brushstrokes to a picture of uterine cancer that rises dramatically with obesity and follows a negatively affected course.

Uterine cancer patients have been shown to be overweight or obese in 57 percent of cases. Research predicts that from 2010 to 2030, uterine cancer rising alongside obesity will increase by 55 percent. Studies also show that each 5-unit increase in body mass index raises the risk of developing uterine cancer by 50 percent. Cancer-related mortality in individuals with a body mass index of 30-35 is approximately 2.5 times that of normal individuals; when body mass index exceeds 40, this rises to as much as 6.25 times. Despite these striking data, a study of 1.545 healthy women found that 58 percent did not know obesity increased uterine cancer risk. Awareness among people with cancer was also inadequate, at 53.5 percent. This picture exposes serious neglect in informing individuals; all healthcare professionals, especially oncologists, must fulfill their responsibility to provide information. Studies have shown that individuals informed about obesity by their physicians make efforts to lose weight.

Mechanisms through which obesity affects uterine cancer

Adipose tissue is a complex endocrine organ containing many different cells, such as fat cells, immune cells and nerve cells, which secrete hormones and substances affecting the entire body. The effects of these hormones and substances on uterine cancer fall under 3 main headings.

1. Estrogen secretion:

In premenopausal women, estrogen is secreted mainly by the ovaries and controlled cyclically; after menopause, tissues outside the ovaries, particularly adipose tissue, become its principal source. Activity of aromatase, the enzyme enabling estrogen synthesis, increases with age and the amount of adipose tissue, while the amount of estrogen-binding protein decreases, increasing free (active) estrogen. Estrogen increased through these mechanisms both accelerates the increase in uterine cell numbers and creates the genetic basis of cancer by causing DNA strand breaks.

2. Insulin and insulin-like growth factor (IGF-1)

In healthy premenopausal individuals, IGF-1 released under estrogen’s influence enables uterine cells to grow in a monthly cycle. Insulin and IGF-1 levels rising with obesity cause uncontrolled growth and thickening of the uterus. During this process, activity of insulin and insulin-like growth factor receptors and their intracellular pathways also increases abnormally. This substantial rise in proliferation signals (MAPK and PI3K pathways), together with reduced activity of tumor suppressor genes (PTEN), represents another pathway laying the groundwork for cancer.

3. Inflammation and adipokines

Adipose tissue secretes adipokines , substances involved in regulating cell metabolism and in chronic (long-term = persistent) inflammation . Adipokines such as leptin and interleukin-6 suppress insulin signaling, cause insulin resistance and lead to proliferation and growth of uterine cells. Cellular stress resulting from inflammation also triggers cancer by causing genetic damage. Unlike these inflammatory adipokines, adiponectin increases the amount of the protein to which estrogen binds (SHBG), reducing free estrogen and thereby protecting against estrogen-stimulated uterine cell proliferation.

Considering all these mechanisms, let us examine approaches to prevention and treatment with a broader understanding of uterine cancer:

Lifestyle changes

Given the strong association between obesity and uterine cancer, healthy weight, a healthy diet and exercise appear at the top of the prevention list. Although some dietary studies have observed no effect of eating patterns on cancer, results from 2 large studies (meta-analyses) indicate that high-glycemic-index diets, which rapidly raise blood sugar, substantially increase uterine cancer risk; according to 3 case-control studies, the Mediterranean dietmay reduce uterine cancer risk. More numerous and robust studies are needed to make definitive statements about exercise.

Surgical approaches

When seeking a surgical approach to weight loss, the first option encountered is obesity (bariatric) surgery . According to one study, individuals who lose weight through bariatric surgery have a uterine cancer risk 60 percent lower than obese individuals. Lifestyle changes are considered before surgery; if they are insufficient, surgery is among the options that may be considered for some individuals.

Medicines

Studies have shown that insulin increases with obesity, that increased estrogen acts as an accelerator for cell growth and proliferation, and that progesterones, which act as a kind of “brake”, are low in obese women. In light of this information, the progesterone content of oral contraceptives has a protective effect against uterine cancer. A recent meta-analysis reviewing 36 studies suggests that 5 years of oral contraceptive use reduces uterine cancer risk by 24 percent. This protective effect persists for 30 years after oral contraceptives are discontinued. Intrauterine devices (IUDs) are associated with a uterine cancer risk 19 percent lower in users than in nonusers. This effect is more pronounced in those who use them for longer than 10 years.

In conclusion; obesity plays a leading role in uterine cancer, as in many other cancers. Estrogen-mediated cancer mechanisms increase the risk not only of uterine cancer but also of breast, ovarian, esophageal, kidney, colorectal and pancreatic cancers. The most effective treatment is preventing cancer from developing, with lifestyle changes as the first approach. When this first step is insufficient, options such as bariatric surgery are considered. Minimally invasive surgical methods, such as laparoscopy, are preferred for these procedures because of the usual surgical difficulties in obese patients and their numerous accompanying diseases. Physicians, particularly oncologists, have major responsibilities in managing this process, and particular care must be taken to provide patients with appropriate information.