Ovarian cancer is associated with a high mortality rate in comparison with other cancers.
In the United States, the incidence of ovarian cancer is estimated to be around 22,200
annually. About 14,000 of these women are expected to die of the disease 1]. In Germany the corresponding figures are 7400 and 5500 2]. This high mortality rate is mainly the consequence of ineffective early detection
or screening programs. Most of the cancers are diagnosed at advanced stages. Uterine
endometrial cancer is the most frequent type of gynecological cancer. In Germany,
there are approximately 11,600 new diagnoses every year and 2400 disease-related deaths
2]. Although the mortality due to endometrial cancer is fairly low, there are no established
early detection methods or screening programs for this disease. Earlier detection
would result in much less invasive surgery and less use of radiotherapy and chemotherapy,
leading to substantial benefits for the patients.
With regard to ovarian cancer, effective risk-reducing strategies have been described.
Bilateral salpingo-oophorectomy has been shown to reduce the risk among BRCA mutation carriers by 71–96 % 3]–5]. Numbers of live births, oral contraceptive use, and tubal ligation are also associated
with a significant reduction in the lifetime risk of ovarian cancer.
There are no established screening programs for endometrial cancer, but risk-modifying
strategies are known that allow the risk of endometrial cancer to be controlled —
such as weight control, physical activity, and no exogenous unopposed estrogen 6]–9].
Risk factors are therefore of special interest for both diseases, since accurate risk
prediction might make individualized early detection or screening programs possible.
Risk factors for ovarian cancer include reproductive behavior and use of hormonal
therapies. Pregnancies and the use of oral contraceptives can reduce the incidence
of ovarian cancer 10]. Mutations in the BRCA1 and BRCA2 genes are reported to lead to a lifetime risk of about 20–40 and 15–25 %, respectively
11]. Large-scale genotyping efforts have recently identified and confirmed a total of
11 low-penetrance risk loci that are common in the population 12]–20].
Endometrial cancer risk factors include hormonal and metabolic factors such as obesity,
tamoxifen use, diabetes, hypertension, and high dietary fat consumption 21]. With regard to genetic risk factors, endometrial cancer is the most common malignancy
in women, with mutations associated with Lynch syndrome 22]. Genome-wide association studies have identified some low-penetrance loci, but large-scale
confirmation studies are still pending 23]–25].
In this study endometriosis is evaluated as a risk factor for ovarian- or endometrial
cancer. Endometriosis is a chronic disease that affects 4–30 % of all women during
the reproductive age 26]–28]. Furthermore it is one of the most frequent gynecological diseases. However it can
reasonably be assumed, that the prevalence is about 10 % 28]. The pathogenesis of endometriosis is considered to be complex. Historically a metaplastic
transformation of peritoneal cells or the still favourably retrograde menstruation
of cells through the tubes into the peritoneal cavity are discussed 29]. On a molecular level different pathways such as the estrogen and progesterone pathway,
vasculogenesis, sphingolipids, prostaglandins, and cytokines appear to be involved.
Pelvic pain during menstruation is the main symptom in patients with endometriosis.
Other symptoms can be chronic lower abdominal pain, dysuria, dyschezia and/ or dyspareunia.
The disease is characterized by endometrial cells outside the uterus and is located
mainly in the retrouterine pouch. The diagnosis occurs in gynecological examination
and especially during laparoscopic surgeries with histological verification 30]. Therapy options comprise mainly medication and surgical therapy. The surgical removal
of the lesion is often the first line therapy 31].
An association between endometriosis and both diseases has been suggested, and in
the case of ovarian cancer the connection is clearly established 32]–35]. Patients with endometriosis tend to be younger and to be diagnosed at earlier stages
and with lower-grade ovarian cancer lesions 36], 37]. With regard to endometrial cancer, the evidence is less clear. A reduced risk of
endometrial cancer was even found in a nested case–control study including 39 patients
with endometrial cancer and 211 controls (OR 0.58; 95 % CI, 0.42 to 0.81) 37]. In a different nested case–control study, patients were found to have a relative
risk (RR) of 1.23 (95 % CI, 0.63 to 2.38) 38]. However, most of the relevant studies only include a small number of events, so
that definitive conclusions about associations cannot as yet be drawn 39]–42].
The aim of the present case–control study was to investigate the extent to which a
medical history of endometriosis represents a risk factor for ovarian or endometrial
cancer in addition to age, body mass index (BMI), number of pregnancies, and previous
oral contraceptive (OC) use.