August 10, 2021

Obesity Fuels Rise in Endometrial Cancer (cancer of uterus)

Worldwide, obesity has become a major public health crisis. Although smoking is the most common cause of death that can be prevented, obesity is the second most common.

Endometrial cancer is the most common invasive neoplasms of the female reproductive system in most developed countries with increasing incidence in urban India.

Overweight and obesity not only increase the risk of cardiovascular disease and type-2 diabetes, but also are now known risk factors for a variety of cancer types. Among all cancers, increasing body mass index is most strongly associated with endometrial cancer incidence and mortality but lacks the awareness.

The most frequently mentioned risk factors, which are associated with the occurrence of endometrial cancer are obesity, infertility, high blood pressure, diabetes, liver disease, hormone active tumors of the ovary, and the use of external estrogen.

Obesity is not only associated with increased incidence of endometrial cancer but has also been related to ovarian, breast and colon cancers. It may also be linked with other cancers, including esophageal, pancreatic and kidney (renal).

RELATIONSHIP BETWEEN OBESITY AND CANCER; MECHANISM HOW OBESITY FUELS CANCER

Obesity is defined by the World Health Organization as body mass index> 30 kg / m2 (BMI> 30 kg / m 2 ). In obese patients with overweight from 9.5 to 23 kg develops three times more often endometrial cancer compared to women with normal weight, those over 23 kg overweight frequency of occurrence increases tenfold.

Obese women definitely have an increase in estrogen, which is a hormone that makes some cancers grow.

The association between obesity and endometrial cancer begins with visceral fat, a complex endocrine organ whose components secrete an array of adipokines that induce intermediate effects leading to increased endometrial proliferation and promotion of tumorigenesis. Additionally, adipose tissue contains mesenchymal cells that can be recruited to support tumor growth and progression.

In premenopausal women, cyclic ovarian expression of estrogen further stimulates endometrial proliferation. After menopause, peripheral tissues, especially adipose tissue (fat), becomes the principal site of estrogen synthesis.

 Estrogen and it’s metabolites act to interact with DNA to produce an accumulation of double-stranded DNA breaks to contribute to genetic instability which finally leads to tumor formation.

Type 2 diabetes, also strongly associated with obesity, results in elevated levels of insulin and insulin-like growth factor (IGF)-1, as well as hyperglycemia, all of which contribute to endometrial cancer pathogenesis. In the endometrium, insulin and IGF-1 are characterized by hyperactivity and increased signaling in pathways associated with the development of endometrial cancer.

Obesity also stimulates production of a variety of pro-inflammatory adipokines and cytokines that increase endometrial cancer risk.

So, molecular mechanism of obesity contributing to increased incidence of cancer is fairly well understood.

WHAT SHALL WE DO?

It is important to realize that a large weight loss will reduce cancer risk.

Life style modifications, dietary changes, regular exercises should be inculcated to maintain healthy body weight. Multiple interventions have demonstrated efficacy to ameliorating obesity and, by extension, associated endometrial cancer risk.

Bariatric surgery has demonstrated the ability to achieve dramatic and sustainable weight loss in obese individuals. More specifically, a recent meta-analysis of six observational studies showed a 60% reduction in endometrial cancer risk among obese women who underwent bariatric surgery.

Progestin medications counteract estrogen's proliferative effects on the endometrium, and progestin-containing oral contraceptives have a well established protective effect against endometrial cancer. Intrauterine devices, including those without embedded progestins, also have shown an ability to reduce the risk of endometrial cancer.

Surgery is a principal component of treatment for endometrial cancer. However, obesity can complicate surgery and other clinical management strategies. Obesity not only directly complicates surgery, but obesity-associated medical comorbidities also increase the risk of perioperative complications.

In the end, the message that should be getting out to women is to avoid sedentary lifestyles and maintain a more appropriate/ideal weight, and to plan weight loss for women who are overweight or obese as a means of overall health maintenance.

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