Metabolic risk factors and mechanisms of disease in epithelial ovarian cancer: A review

Abstract

Objective: Epithelial ovarian cancer continues to be the deadliest gynecologic malignancy. Patients with both diabetes mellitus and obesity have poorer outcomes, yet research correlating metabolic abnormalities, such as metabolic syndrome, to ovarian cancer risk and outcomes is lacking. This article reviews the literature regarding metabolic derangements and their relationship to epithelial ovarian cancer, with a focus on potential mechanisms behind these associations.

Methods: PubMed and Google Scholar were searched for articles in the English language regarding epithelial ovarian cancer, obesity, diabetes mellitus, and metabolic syndrome, with a focus on studies conducted since 1990.

Results: Obesity, type II diabetes mellitus, and metabolic syndrome have been associated with poor outcomes in epithelial ovarian cancer. More studies investigating the relationship between metabolic syndrome and epithelial ovarian cancer are needed. A variety of pathologic factors may contribute to cancer risk in patients with metabolic derangements, including altered adipokine and cytokine expression, altered immune responses to tumor cells, and changes in pro-tumorigenic signaling pathways.

Conclusion: More research is needed to examine the effects of metabolic syndrome on epithelial ovarian cancer risk and mortality, as well as the underlying pathophysiologies in patients with obesity, diabetes mellitus, and metabolic syndrome that may be targeted for therapeutic intervention.

Keywords: Diabetes mellitus; Epithelial ovarian cancer; Immune suppression; Metabolic syndrome; Obesity.

Fig. 1

Alterations in adipocytokine expression patterns in obesity and EOC. Green arrows indicate upregulation and red arrows indicate downregulation. Black arrow indicates cytokine recruitment of cells to the tumor microenvironment. Blue arrows with a circular end indicate that the cytokine increases the primary process indicated by the green arrow. NK cell – natural killer cell; IFN-γ – interferon gamma; IGF-1 – insulin-like growth factor 1; IGF-1 R – insulin-like growth factor 1 receptor; TNF-α – tumor necrosis factor alpha; TAM – tumor associated macrophage; HIF – hypoxia inducible factor; IL-6 – interleukin 6; VEGF – vascular endothelial growth factor; OB-Rb – Leptin receptor; EOC – epithelial ovarian cancer.