The dramatic increase in the incidence of uterine cancer observed in recent decades is a direct consequence of the obesity epidemic.
Endometrial cancer, the lining lining the inside of the uterus, is the sixth most common gynecological cancer, with approximately 417,000 new diagnoses made worldwide in 2020. The overall incidence of this cancer is on the rise meteoric rise, with a 132% increase over the last 30 years, mainly in North America where the highest rates in the world are currently observed (87 cases/100,000 women). This disease mainly affects postmenopausal women (61 years old on average) and the aging of the population therefore plays a role in this increase in incidence. However, the proportion of women under 40 with this cancer has also doubled in recent years, indicating that other components of modern lifestyle are contributing to the strong progression of this cancer.
Closely related to overweight
One of these factors is being overweight. Of all cancers, endometrial cancer has the strongest link to obesity: compared to women of normal weight (BMI between 18 and 25), the risk of endometrial cancer is 5 times higher in obese women (BMI greater than 30) and 20 times higher in those who are morbidly obese (BMI of 40). The lifetime risk of endometrial cancer in women with a BMI greater than 40 kg/m is 10-15%, which is equivalent to the lifetime risk of lung cancer in smokers.
Inflammation, estrogen and insulin
Several reasons have been proposed to explain this close link between being overweight and the risk of endometrial cancer:
1) Inflammation. Excess fat causes chronic inflammation (high levels of inflammatory molecules such as IL-6 and TNF-a, among others) which, combined with a decrease in protective immune cells in the uterine lining, creates a climate conducive to the acquisition of mutations that can initiate endometrial cancer.
2) Excess estrogen. In addition to being proinflammatory, obesity also represents a "hyperestrogenic" state, as androgens produced by the adrenals are converted by the aromatase enzyme in fat cells into estrogens.
Estrogens stimulate the growth of endometrial cells and it is well documented that factors associated with increased exposure to these hormones (early menses, polycystic ovary syndrome, menopause after age 55) increase the risk of uterine cancer .
The estrogen imbalance caused by obesity may therefore contribute to the impact of overweight on the risk of endometrial cancer, particularly in postmenopausal women where the absence of natural progesterone does not counterbalance the impact. of excess estrogen on the growth of cells in the uterine lining.
3) Rise in insulin. One of the main metabolic consequences of obesity is to disrupt glucose metabolism by decreasing the efficiency of insulin.
In the short term, the overproduction of insulin by the pancreas compensates for this problem, but the resulting rise in insulin levels has several harmful effects. For example, hyperinsulinemia promotes the growth of endometrial cells by increasing the bioavailability of estrogens and IGF-1, a growth factor that activates an oncogenic pathway involved in the proliferation of cells in the intestinal mucosa.
Overall, we can therefore consider obesity as a hyperestrogenic, hyperinsulinaemic and proinflammatory state that promotes the growth of the endometrium, the accumulation of oncogenic mutations and, ultimately, the development of cancer in this organ. Another example of the multiple imbalances caused by excess weight and the serious consequences that flow from it.
