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Review

Insulinemia, heterogeneity of obesity and the risk of different types of endometrial cancer: existing evidence

Pages 51-64 | Received 05 Oct 2015, Accepted 02 Dec 2015, Published online: 08 Jan 2016
 

ABSTRACT

Due to a number of reasons, endometrial cancer is a point of interest not only for oncologists, but also for a variety of specialists – especially endocrinologists. The endocrinology of endometrial cancer can be firmly divided into two categories – steroid and non-steroid. The steroid approach dominated during several decades due to hyperestrogenization signs observed in some patients. The balance was only regained in the last 15 years, when the role of diabetes and insulin resistance began to draw attention. This review aims to provide an update on connections between insulinemia (insulin resistance) and different obesity phenotypes as well to discuss their relation to development of endometrial cancer, its clinical-morphological features and the increasing number of its molecular-biological subtypes.

Financial & competing interests disclosure

This work was partly supported by Russian Foundation for Basic Research (grant 15-04-00384) received by LM Berstein. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

  • In the last decade we evidenced a worldwide increase in endometrial cancer (EC) incidence; in no small measure it was caused by obesity epidemics expanded concurrently with growing numbers of diabetes mellitus and metabolic syndrome/insulin resistance cases.

  • Obesity is a complex entity not equivalent to excessive body mass; therefore an analysis of its connections to EC development risk, clinical course, prognosis and survival should consider a number of different factors, including the role of diverse obesity types, in particular “standard” (associated with insulin resistance) and “metabolically healthy” (MHO) obesity.

  • Obesity and insulin resistance can influence clinical and morphological EC characteristics; their influence is complex, some of the conclusions in this area are contradictory and – as mentioned above – at least partly can be explained by heterogeneity of obesity.

  • Data presented in recent publications on hormone-metabolic risk factors of two “classical” types of EC are somewhat at odds; the stated judgments display evident variation from attributing specific EC type-associated risk factors to finding no significant difference.

  • Besides the reasons already mentioned, this variability may be caused by EC molecular and biological diversity, which may express the need for new and more complex classification replacing the one currently used (type I and type II EC) and, as well, be attributed to gradual EC evolution some signs of which are observed in the last few decades.

  • Besides the study of genetic and epigenetic factors, the understanding of different EC subtypes could be driven by comparison of endometrial stem cells and adipose-derived stem cells (brown and white fat tissue precursors) populations in obese patients and patients with normal body mass.

  • The issue of whether the influence of obesity, hyperinsulinemia and insulin resistance on EC risk and clinical course is mediated by DNA damage or DNA repair defects requires further investigation.

  • The most important practical consideration based on the accumulating body of EC data is a necessity of a multidisciplinary team (including oncologists as well as endocrinologists) for preventive and therapeutic recommendations algorithm creation based on our present and future knowledge of relations between hormone-metabolic disturbances (in particular, obesity, its phenotypes, insulin resistance, diabetes mellitus) and certain EC subtypes (see ).

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