Sporadic Epithelial ovarian tumors

# An attempt to explain the origin of carcinogenesis in sporadic epithelial carcinoma

# Obesity a risk factor for epithelial cancer
- A British study comprising of 1.2 million women found that incidences of epithelial ovarian cancer were higher among women with BMI >30 as compared to women with normal BMI, with risk increasing with incremental increase in BMI. A meta-analysis conducted Olsen et al.also found an increase risk for epithelial ovarian cancer in obese women.
- It has been hypothesized that waist to hip ratio provides a better risk determination for epithelial ovarian cancer because of more accuracy in assessing true visceral fat deposition but remains to be validated.
- The time at which women develop obesity during their life may be a key factor for increased risk for epithelial ovarian cancer. Multiple studies indicate that increased BMI in adolescence and/or early adulthood may confer a greater risk for developing epithelial ovarian cancer.
- Another study postulates that duration and severity of obesity is also associated with increased risk for epithelial ovarian cancer and few others postulate that association of obesity with epithelial ovarian cancer is greater in premenopausal women than post-menopausal.
- Another meta-analysis demonstrated that obesity is associated with not only an increased risk for epithelial ovarian cancer but also with decrease in overall survival and ovarian-cancer specific survival. Another study also showed an increase in ovarian cancer- related mortality in obese women.

# Diabetes mellitus and the risk for epithelial ovarian cancer
- While conflicting data is present for association of diabetes mellitus and an increased risk for epithelial ovarian cancer, multiple studies, however,  demonstrated diabetes as an independent risk factor for increased mortality in epithelial ovarian cancer.
- Findings in some studies indicate a greater risk for epithelial ovarian cancer in diabetic women while some suggest an increased risk only in pre-menopausal women, and some suggest no increase in risk for epithelial ovarian cancer at all.

# Metabolic syndrome and the risk for epithelial ovarian cancer.
- The case for metabolic syndrome to be associated with an increased risk for epithelial ovarian cancer is similar to that of diabetes mellitus. There has been a fewer studies on association between metabolic syndrome and epithelial ovarian cancer and the results are conflicting with some found an increased risk for epithelial ovarian cancer in women with metabolic syndrome while some found no association.
- But an association of metabolic syndrome with increased ovarian cancer-related mortality was found in these studies. These studies however had limitation of lack of racial diversity because the study sample comprised only of Caucasian women.

# Pathogenesis of epithelial ovarian cancer associated with metabolic abnormalities
- The work on mechanisms linking metabolic abnormalities to epithelial ovarian cancer is not yet complete and the way by which these abnormalities confer a greater risk for epithelial ovarian cancer is not well-understood but several theories have been put forward.
- The most significant of these theories include role of cytokines and adipokines, immune cells, and aberrant signaling pathways in association with increased risk for epithelial ovarian cancer in women with metabolic derangement.

## Cytokines and adipokines

## Immune cells
- Immune cells may have a pro or anti-tumor effect, depending on the cell type. Metabolic risk factors may alter these cell types and their functions to have a promoter effect in initiation and progression of epithelial ovarian tumors.
- The table below provides a short overview of possible role of immune cells in pathogenesis of epithelial ovarian tumors.

## Hormones, signaling pathways in pathogenesis of epithelial ovarian cancer and their link with metabolic risk factors
- Hormones and signaling pathways that may play a role in pathogenesis of epithelial ovarian cancer with link to metabolic abnormalities are summarized below in table: