Ovarian cancer is the most common cause of cancer death due to gynecologic tumors in the United States. More than 200,000 women in the world are estimated to develop ovarian cancer every year and about 100,000 die from the disease. The lifetime risk of a woman developing epithelial ovarian cancer is 1 in 70. While believed to arise from the surface of the ovaries, many of these actually originate in the fallopian tubes.
The precise cause of ovarian cancer is unknown. However, several risk and contributing factors (including both reproductive and genetic factors) have been identified.
Risk Factors for Ovarian Cancer
Reproductive factors
1. Live births or pregnancies that are of longer duration, regardless of outcome, lower one’s risk of ovarian cancer. The risk of the most common type of ovarian cancer is increased in women who have not had children and possibly those with early menarche or late menopause. Women who have been pregnant have a 50% decreased risk for developing ovarian cancer compared with women who have never had a child. Multiple pregnancies offer an increasingly protective effect.
2. Oral contraceptive use decreases the risk of ovarian cancer significantly.
These factors support the idea that risk for ovarian cancer is related to ovulation.
Thus, the probability of ovarian cancer may be related to the number of ovulatory cycles, and conditions that suppress the ovulatory cycle (such as birth control pills) may play a protective role. However, fertility drugs to cause ovulation have not been shown to increase the risk of ovarian cancer
Genetic factors
1. Family history plays an important role in the risk of developing ovarian cancer. The lifetime risk for developing ovarian cancer is 1.6% in the general population. This compares with a 4-5% risk when 1 first-degree family member is affected, rising to 7% when 2 relatives are affected. From 5-10% of cases of ovarian cancer occur in an individual with a family history of the disease.
Hereditary ovarian cancer occurs at a younger age (approximately 10 years younger) than nonhereditary epithelial ovarian cancer, but the prognosis may be somewhat better.
2. Evidence from the Cancer Genome Atlas Network showed that some types of ovarian tumors and breast tumors shared a number of genetic characteristics, such as the types and frequencies of gene mutations, suggesting that ovarian and breast cancer may have a related cause and potentially similar responsiveness to some of the same therapies.
At least two syndromes of hereditary ovarian cancer are clearly identified, involving either (1) disorders of the genes associated with breast cancer, BRCA1 and BRCA2, or (2) more rarely, genes within the Lynch II syndrome complex.
Breast/ovarian cancer syndrome is associated with early onset of breast or ovarian cancer. Inheritance can come from either parent.
Most cases are related to the BRCA1 gene mutation. BRCA1 is a tumor suppressor gene that inhibits cell growth when functioning properly meaning that a mutation of it causes it to not function properly.
Approximately 1 person in 4000 in the general population carries a mutation of BRCA1. Some populations have a much higher rate of BRCA1 and BRCA2 mutations, especially Ashkenazi Jews.
In families with 2 first-degree relatives (mother, sister, or daughter) with premenopausal epithelial ovarian cancer, the likelihood of a female relative having an affected BRCA1 or BRCA2 gene is as high as 40%.
Individuals with a BRCA1 gene mutation have a 50-85% lifetime risk of developing breast cancer and a 15-45% risk of developing epithelial ovarian cancer. Those with a BRCA2 gene mutation have a 50-85% lifetime risk of developing breast cancer and a 10-20% risk of developing epithelial ovarian cancer.
Families with BRCA2 mutations are at risk for developing cancer of the prostate, larynx, pancreas, and male breast.
Families with Lynch II syndrome or hereditary (non-polyp associated) colorectal cancer are characterized by a high risk for developing colorectal, uterine, stomach, small bowel, breast, pancreas, and ovarian cancers.
Women with a history of breast cancer have an increased risk of epithelial ovarian cancer.
Hormone therapy
The risk for ovarian cancer is increased with hormone therapy, regardless of duration of use, formulation, estrogen dose, regimen, progestin type, and administration route.
Current users of hormones had incidence rate that was 38% higher for all ovarian cancers of compared to women who never took hormone therapy. Risk declined as years since last hormone use increased.
Other factors
· Childhood obesity and an increased adult height and body mass index (BMI) are associated with a modestly increased risk of ovarian cancer. Obesity is linked to higher overall estrogen levels due the conversion of androgens to estrogens in fat stores.
· Endometriosis has been linked to an increased risk of ovarian cancer.
· The use of talcum powder on the vulva and perineum may be associated with increased risk of epithelial ovarian cancer.
· High lactose consumption has been associated with increased risk of ovarian cancer, but evidence linking specific dairy products with ovarian cancer remains contradictory.
· Women who experienced six or more symptoms of post-traumatic stress disorder (PTSD) at some point in life had a twofold greater risk of developing ovarian cancer compared with women who never had any PTSD symptoms and this could occur even decades after the traumatic event.
Signs and Symptoms of Ovarian Cancer
Epithelial ovarian cancer presents with a wide variety of vague and nonspecific symptoms, including the following:
· Bloating; abdominal distention or discomfort
· Pressure effects on the bladder and rectum
· Constipation
· Vaginal bleeding
· Indigestion and acid reflux
· Shortness of breath
· Tiredness
· Weight loss
· Early satiety
Symptoms independently associated with the presence of ovarian cancer include pelvic and abdominal pain, increased abdominal size and bloating, and difficulty eating or feeling full.
Symptoms associated with later-stage disease include gastrointestinal symptoms such as nausea and vomiting, constipation, and diarrhea. Presentation with swelling of a leg due to venous thrombosis is not uncommon.
Diagnosis
Most expert governing bodies like the FDA and National Cancer Institute recommend against screening (with serum CA-125 level or transvaginal ultrasonography) for ovarian cancer in the general population. The reasons cited are the lack of mortality benefit with screening, and potential harms relating to false-positive test results. However, any persistent pelvic symptoms warrant an exam and ultrasound.
In cases in which the diagnosis is uncertain, consider the following imaging studies:
· Pelvic ultrasonography
· Pelvic and abdominal computed tomography (CT) scanning
· Pelvic and abdominal magnetic resonance imaging
· Chest radiography: Routine imaging to exclude lung metastases
· Mammography: Part of preoperative workup for women older than 40 years who have not had one in the preceding 6-12 months; estrogen-producing tumors may increase the risk of breast malignancies, and breast cancers can metastasize to the ovaries and are often bilateral
1. Goff BA, Mandel LS, Drescher CW, Urban N, Gough S, Schurman KM, et al. Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer. 2007 Jan 15. 109(2):221-7.
2. Ryerson AB, Eheman C, Burton J, McCall N, Blackman D, Subramanian S, et al. Symptoms, diagnoses, and time to key diagnostic procedures among older U.S. women with ovarian cancer. Obstet Gynecol. 2007 May. 109(5):1053-61.
3. [Guideline] Henderson JT, Webber EM, Sawaya GF. Screening for Ovarian Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2018 Feb 13. 319 (6):595-606.
4. The FDA recommends against using screening tests for ovarian cancer screening: FDA Safety Communication. U.S. Food & Drug Administration. Available at https://wayback.archive-it.org/7993/20171103022558/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm519540.htm. September 7, 2016; Accessed: June 15, 2019.