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.

Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway

“…Moreover, diabetes is also associated with poor prognosis and survival of patients suffering from these cancers [ 6 , 7 ]. There are a few reports that provide strong evidences about the positive association of diabetes with the development of ovarian cancer [ 8 , 9 ]. The association between diabetes and cancer is complex.…”

Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium

“…Obesity may potentiate an ovarian cancer toward an aggressive pathway via its impact on the metabolic milieu or may influence disease aggressiveness by providing a permissive local microenvironment for metastases, reducing efficacy of treatment, or poor post‐surgical performance. The associations between BMI and adipokines, insulin resistance and the metabolic syndrome, and oxidative stress and chronic low‐grade inflammation are well described; in turn, these factors have been hypothesized to be associated with ovarian cancer progression . Furthermore, adiposity is associated with higher endogenous estrogen concentrations, as a result of an upregulation of aromatase activity, particularly in postmenopausal women .…”

“…The associations between BMI and adipokines, insulin resistance and the metabolic syndrome, 27 and oxidative stress and chronic lowgrade inflammation 28 are well described; in turn, these factors have been hypothesized to be associated with ovarian cancer progression. [29][30][31][32][33] Furthermore, adiposity is associated with higher endogenous estrogen concentrations, as a result of an upregulation of aromatase activity, 34 particularly in postmenopausal women. 35,36 However, the trends we observed for HT use were in the opposite direction of those observed for BMI, providing no support for endogenous estrogens as an intermediate mechanism.…”

The impact on high‐grade serous ovarian cancer of obesity and lipid metabolism‐related gene expression patterns: the underestimated driving force affecting prognosis

“…Epidemiological evidence now points to the negative impact of obesity on ovarian carcinogenesis . The low‐grade chronic inflammatory state characteristic of this condition not only acts as an inducing factor but can also control cancer cell behaviour and facilitate its adaptive evolution through the clinical course of the disease . Our group and other researchers have recently provided evidence that overweight and obese ovarian cancer patients have worse outcome than leaner counterparts .…”