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Ovarian cancer
Description
An in-depth report on the causes, diagnosis, treatment, and prevention of ovarian cancer.
Causes
About 20,180 new cases of ovarian cancer are expected in the United States in 2006. Evidence suggests that the incidence of ovarian cancer is declining. The average age for the onset of ovarian cancer is about 60, although ovarian cancer can develop in women from the ages of 20 to 90. The lifetime risk of ovarian cancer in women with no family history of the disease is approximately one in 70 (1.4%).
Women with a history of ovarian cancer in one first-degree relative (mother or sister) have an overall 5% risk of developing the disease, but it may be higher in women with specific genetic factors. The majority of women with ovarian cancer have no family history of the disease, however, meaning that genetic inheritance is not the only risk factor.
Genetic mutations causing abnormal cell growth and differentiation are the basis for all cancer. The great majority of genetic defects that cause cancer are due to unknown causes. Most likely overexposure to environmental assaults or errors that occur during cell division play a role in many cases.
The Role of Hormones and Ovarian Stimulation
Several circumstances that create hormonal changes may increase the risk of ovarian cancer.
Number of Ovulations. Risk of ovarian cancer is directly related to the number of times a woman ovulates, which is indicated by the total number of menstrual periods she has had. A lower number of ovulations occur when the menstrual periods are shut off (as in pregnancy), so the risk of developing ovarian cancer is reduced.
The following women have a lower risk for ovarian cancer:
- Women with a history of multiple pregnancies.
- Women who took birth control pills (these shut off the menstrual period).
- Women who breast-fed. (The body usually does not release eggs while a woman is breast-feeding.)
Some researchers theorize that ovarian cancer develops in women with a higher number of ovulations because of persistent damage to the epithelial cells as the egg passes through during ovulation. Researchers postulate that the recurring cell division needed to heal these tiny wounds to the ovaries, month after month and year after year, creates opportunities for errors in cell reproduction that lead to the formation of cancerous cells. Therefore, the more ovulations, the more risk of ovarian cancer. Ovulation temporarily ceases during pregnancy, breast-feeding, and birth control pill use.
Gonadotropins and Fertility Drugs. Gonadotropins are hormones produced in the pituitary gland that stimulate the ovaries to secrete estrogen and cause the follicles to produce and release eggs.
The pituitary is a gland attached to the base of the brain which secretes hormones that govern the onset of puberty, sexual development and reproductive function.
In a few studies, elevated levels of gonadotropins have been associated with an increased risk for ovarian cancer. These hormones are the basis for many fertility drugs, including human menopausal gonadotropin (Pergonal, Repronal, Metrodin) and clomiphene (Clomid, Serophene). Although there has been concern about an increased risk for ovarian cancers in women, a growing body of evidence is finding no higher risk from the drugs themselves. Instead, evidence suggests that ovarian cancers are most likely caused by factors contributing to the infertility -- not the drugs used to treat it.
Hormone Replacement Therapy (HRT). Although some studies have reported a weak increased risk for certain ovarian cancers in women taking HRT, others have found no association either with short- or long-term use of HRT.
Inherited Genetic Factors
Family history plays a role in 5 - 10% of women who have ovarian cancer. Certain genes are being investigated and identified that are responsible for some of these cases. Depending on the particular genetic type, the lifetime risk for ovarian cancer in women who carry these genes ranges from 16 - 65%.
BRCA1 and 2 Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are now believed to be responsible for 30 - 50% of breast cancers, ovarian cancers, or both in patients with a strong family history of these cancers.
According to some studies, the risks are as follows:
- Studies indicate that about 25 - 40% of women who carry the abnormal BRCA1 gene may develop ovarian cancer.
- The risk for women with the BRCA2 gene mutation is generally believed to be lower, about 9 - 15%.
The mutated genes are linked to an even higher risk for developing breast cancer. These mutations are present in only about 0.5% of the U.S. population overall but occur in about 2.5% of all Jewish women of Eastern European (Ashkenazi) descent. These mutations are not restricted to the Ashkenazi population and may occur in women of any ethnicity, including women of Asian and African descent.
Either a mother or father can pass down BRCA mutations to the daughter. These mutations may also occur in 5 - 10% of ovarian cancer patients who have no family history of breast or ovarian cancer. A number of studies have suggested that women with BRCA-mutated ovarian cancers tend to have better survival rates than other women.
A reassuring 2005 study in the Journal of the National Cancer Institute indicated that women who have a family history of breast cancer, but no history of BRCA genetic mutations, are not at increased risk for ovarian cancer.
Other Genetic Mutations. Women who carry the hereditary nonpolyposis colorectal cancer (HNPCC) gene have about a 9% chance of developing ovarian cancer.
Identifying and Screening High-Risk WomenRisk Factors for Inherited Ovarian Cancer Women are considered at high risk for ovarian cancer if they have:
When a woman describes her family history to her doctor, she should include the history of cancer in women on both the mother's and the father's side. Both are significant. Screening High-Risk Women It is now possible to test for genetic mutations in the BRCA1 and BRCA2 genes and for hereditary nonpolyposis colorectal cancer (HNPCC) and Peutz-Jeghers syndrome in high-risk women. Any positive result raises difficult issues:
Screening Guidelines for BRCA Genes In 2005, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines for BRCA testing. While women at high risk should be tested, the USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA 1 or 2 genetic mutations). |
Sporadic Genetic Factors
Most ovarian cancers are the result of genetic mutations that are not inherited but occur from environmental or other factors that cause damage to genetic material over time. Such genetic changes are referred to as sporadic (as opposed to inherited). Genetic alterations that have been observed in ovarian cancers involve the p53 tumor suppressor gene, the HER2/neu gene, and the PIC3KA gene.
Ethnic Factors
Some research indicates that ovarian cancer occurs more often in North America and Northern Europe and among middle to upper socioeconomic class women from highly industrialized countries. Ovarian cancer is also much more common in Caucasian women than in African American women. Japan has a low, but rising, number of ovarian cancer cases. One study observed that when Japanese women immigrate to the United States, they and their daughters have an incidence of ovarian cancer that approaches that of Caucasian women, although another study did not support such findings.
Other Factors
Pregnancy. Women who have never had children are more likely to develop ovarian cancer than women who have had children. The more children a woman has had, the lower her risk for ovarian cancer.
Obesity . Obesity may increase the risk of developing more aggressive types of ovarian tumors. A 2006 study indicated that a higher body mass index (BMI) was associated with poorer survival.
Endometriosis. Women with endometriosis may have some higher risk for ovarian cancer. However, endometriosis is very common and ovarian cancer is not, so the risk is still very low. Some research suggests that ovarian cancer associated with endometriosis may differ from most ovarian cancer cases and, in fact, have a better outlook.
Fat Intake. Fats have been under scrutiny for some time for putting some women at higher risk for ovarian cancer. A 2001 review reported an association between a high intake in animal fats and a greater risk. However, other studies on this subject have found no correlation between fat intake and ovarian cancer.
- Review Date: 9/1/2006
- Reviewed By: Harvey Simon, M.D., Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.
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