Abstract
Background
Ovarian cysts represent a common condition among women. Epidemiologic studies are inconsistent in determining if women with cysts are more likely to develop endometrial cancer (EC) regardless of overweight/obesity. We investigated the combined role of cysts and body mass index (BMI) on EC risk.
Methods
We pooled data from three case-control studies conducted in Italy and Switzerland on 920 women with EC and 1700 controls. The prevalence of cysts was 5% among both cases and controls, with 63% of cases being overweight/obese. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression models, adjusting for potential confounders. We conducted stratified analyses according to BMI, and estimated the interaction between cysts and BMI; we carried out additional analyses according to age at diagnosis of cysts.
Results
Overall, history of cysts was not associated to EC (OR=1.27, 95% CI=0.82–1.97, P = 0.29). Normal weight women reporting cysts had an increased risk of EC (OR=2.49, 95% CI=1.31–4.74), while no such effect was found among overweight/obese women (OR=0.65, 95% CI=0.36–1.18; P for interaction=0.004). The association was limited to women below 65 years of age and was stronger in those who reported cysts at age 48 or older.
Conclusions
Cysts appeared to be a risk factor for EC in lean women but not in overweight/obese ones; these results are consistent with an effect of cysts and obesity on EC along common pathways.
Highlights
- • Few studies investigated the risk of endometrial cancer for ovarian cysts, despite they represent a common condition in women of different ages.
- • This is the first analysis showing an effect modification of body mass index on the association between endometrial cancer and ovarian cysts.
- • Our results add insight on the close association between body mass index and endometrial cancer, where cyst-related conditions may be a confounder.
1
Introduction
Endometrial cancer (EC) is the most common cancer of female reproductive tract in high-income countries .
High endogenous unopposed secretion of estrogen has long been recognized as a major mechanism of endometrial carcinogenesis . Indeed, factors increasing endogenous sex steroid hormones (e.g., obesity, diabetes, nulliparity, hormonal replacement therapy) enhance the risk of EC . Cysts of the ovary are fluid-filled sacs in or on an ovary, which usually form during ovulation. Most ovarian cysts are small and remain asymptomatic; these cysts represent serendipitous findings of a pelvic exam. Symptoms due to cysts include pressure, bloating, swelling and pain in the lower abdomen. Sporadic cysts may represent a potential risk factor of EC. Multiple cysts are a key component of polycystic ovary syndrome (PCOS), an endocrine-metabolic disorder characterized by prolonged anovulation and exposure of the endometrium to the actions of estrogens, unopposed by progesterone, causing a hormonal imbalance which in turn could promote the development of EC .
The estimated prevalence of cysts is around 7% worldwide, reaching around 20% among postmenopausal women . While some studies have identified a link between PCOS and EC, their results were hampered by methodological limitations such as inappropriate adjustment of confounders and small sample size. Few studies investigated the effect of cysts on EC in absence of PCOS , with inconsistent results. We investigated the relationship between cysts and histologically confirmed EC using data from three case-control studies from Italy and Switzerland .
Since overweight/obesity is strongly associated to EC , and the two risk factors may act through common pathways related to hormonal imbalances. we explored the potential interaction between body mass index (BMI) and cysts in determining EC risk.
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