Insulin resistance: a significant risk factor of endometrial cancer

Abstract

Objective: To review the role played by insulin resistance in the development of endometrial cancer.

Methods: Relevant manuscripts and studies were searched on Medline using the terms endometrial cancer, insulin resistance, obesity, adipokine, C-peptide, leptin, adiponectin, plasminogen activator inhibitor-1, insulin, PI3K/Akt, Ras/MAPK and metformin alone or in combination.

Results: Epidemiological studies have shown that insulin resistance is an important potential risk factor of endometrial cancer, and several research studies have been undertaken to determine the mechanism underlying its link to this malignant disease. Risk factors of insulin resistance, such as the inflammatory mediators, adipokines adiponectin, leptin and plasminogen activator inhibitor-1 and excessive androgen are also risk factors of endometrial cancer. High levels of insulin induced by insulin resistance have been found to exert direct and indirect effects that contribute to the development of endometrial cancer. Insulin directly promotes cell proliferation and survival through the PI3K/Akt and Ras/MAPK pathways. Moreover, the network among insulin, estrogen and insulin-like growth factor-1 also contributes to the development of endometrial cancer. Indirectly, insulin leads to changes in sex hormone levels, including increases in the levels of estrogen. Additionally, a small number of studies suggested that metformin, an insulin-sensitizing agent, has therapeutic potential for endometrial cancer.

Conclusions: This evidence suggests that insulin resistance plays a central role in endometrial cancer development. Understanding the relationship between insulin resistance and endometrial cancer may supply new ideas to fight this malignancy. Furthermore, combating insulin resistance may be a useful preventive and therapeutic strategy for endometrial cancer.