Risk Factors for Ovarian Cancer
The biologic events that lead to ovarian cancer remain unknown. Several factors (e.g., hormonal, environmental, and genetic variables) may play a role, although all women are at risk for developing this disease.
A number of specific risk factors are associated with epithelial ovarian cancer, although these factors are not linked with more rare forms of ovarian cancer, such as germ cell tumors. Unfortunately, most ovarian cancer cases occur without identifiable risk factors.
Risk factors include the following:
- Family history of ovarian cancerA woman's family history is the most important factor to be considered when estimating her risk for ovarian cancer. Research suggests that a woman has as high as a 50 percent risk of getting ovarian cancer if two or more first-degree (e.g., mother, sister, daughter) or second-degree (e.g., grandmother, aunt) relatives have had this disease. Researchers have identified three distinct ways in which ovarian cancer can be inherited:
AgeThe risk for developing ovarian cancer increases with age. Most cases occur after menopause, which usually takes place around the age of 51. Over 50% of all ovarian cancers occur in women older than age 65.
Menstrual history/pregnancy history/infertilityMany experts believe that there is a relationship between the number of menstrual cycles that a woman has in her lifetime and her risk of ovarian cancer. That is, the risk of ovarian cancer is increased in women who began to menstruate before age 12 and/or experienced menopause after age 50. Also, never having given birth (nulliparity) is a risk factor for the development of ovarian cancer, as is having a first child after age 30. In other words, women who have never been pregnant have a higher risk of ovarian cancer than those who have been pregnant. Multiple pregnancies have an increasingly protective effect. Similarly, women who take or have taken birth control pills have a 40 to 50 percent decreased risk of ovarian cancer. It is thought that the protective effects of pregnancy, birth control pills, and breast feeding are related to the suppression of ovulation, that is, the fewer ovulatory cycles that a woman completes, the lower are her chances of developing ovarian cancer.
Fertility drugsWomen who have used ovulation-stimulating fertility medications such as clomiphene citrate (Clomid®) and menotropins (Pergonal®) have a slightly increased risk of ovarian cancer. Yet ovarian cancer risk returns to normal in women who become pregnant while taking such drugs. The type of ovarian tumors most often associated with the use of fertility drugs are tumors of low malignant potential (LMP tumors).
High-fat Western dietDiets that are high in meat and animal fats have been linked to the development of ovarian cancer. Such diets are more common in industrialized Western countries, which have higher rates of ovarian cancer than undeveloped nations. Obesity also increases the risk, especially in women who have never given birth.
Talcum powderSome research indicates that there is an increased risk of ovarian cancer among women who apply talcum powder to the genital area or sanitary napkins. Talc (an ingredient in many body powders and feminine hygiene products) has been implicated in ovarian cancer because in the past, it was sometimes contaminated with asbestos, a known cancer-causing substance. Although such products are now required to be asbestos-free, proof of their safety or carcinogenicity (cancer-causing potential) has yet to be determined.
Acquired genetic mutationsResearchers have not yet been able to identify specific environmental factors that are responsible for the genetic mutations (changes) causing ovarian cancer. Such acquired genetic mutations, rather than inherited genetic mutations, make up the bulk of DNA defects that are associated with ovarian cancer. The identification of genetic changes may help to predict a woman's prognosis. Ovarian cancers, like all cancers, may be caused by DNA mutations that alter oncogenes (genes that promote cancer cell division), tumor suppressor genes (cancer-preventing genes), or other genes. In particular, acquired mutations of the HER2 oncogene or the p53 tumor suppressor gene may be associated with a higher risk of ovarian cancer. A new immunologic treatmentmonoclonal antibody therapythat stops the activity of the HER2 oncogene is being evaluated in clinical trials to determine its usefulness against ovarian cancer.
- Site-specific ovarian cancer syndrome applies to women with two or more first-degree, or first- and second-degree relatives who have had ovarian cancer. This is a rare syndrome in which multiple female family members are affected by the development of ovarian cancer only.
- Breast/ovarian cancer syndrome applies to women who have first-and second-degree relatives with breast and/or ovarian cancers. Breast/ovarian cancer syndrome is a genetic disorder in which women have ovarian cancer that is associated with early onset breast cancer. Women with this syndrome have a mutation (abnormal change) in either the BRCA1 or BRCA2 genes. It is believed that BRCA1 and BRCA2 are tumor suppressor (cancer-preventing) genes parts of the chemical DNA that encodes the body's building blocks. Their usual role is to make proteins that regulate cell growth and repair of DNA in the breast and/or ovaries. Genetic defects make women more susceptible to cancer development in these tissues. By age 70, approximately one-half of all women with inherited BRCA1 mutations will get breast and/or ovarian cancer; women with BRCA2 mutations have a comparable risk of breast cancer.
- Lynch syndrome II (family cancer syndrome) applies to women with female or male relatives who have had nonpolyposis cancer of the colorectal system (disease not associated with polypsmasses that protrude from the intestinal lining), endometrium (lining of the womb), gastrointestinal tract, kidneys, pancreas, ovary, or other sites. Lynch syndrome also is linked with an inherited genetic mutation that lessens the body's ability to prevent cancer.