Do we know what causes ovarian cancer?
We don’t yet know exactly what causes most ovarian cancers. As discussed in the previous section, we do know some factors that make a woman more likely to develop epithelial ovarian cancer. Much less is known about risk factors for germ cell and stromal tumors of the ovaries.
There are many theories about the causes of ovarian cancer. Some of them came from looking at the things that change the risk of ovarian cancer. For example, pregnancy and taking birth control pills both lower the risk of ovarian cancer. Since both of these things reduce the number of times the ovary releases an egg (ovulation), some researchers think that there may be some relationship between ovulation and the risk of developing ovarian cancer.
Also, we know that tubal ligation and hysterectomy lower the risk of ovarian cancer. One theory to explain this is that some cancer-causing substances may enter the body through the vagina and pass through the uterus and fallopian tubes to reach the ovaries. This would explain how removing the uterus or blocking the fallopian tubes affects ovarian cancer risk. Another theory is that male hormones (androgens) can cause ovarian cancer.
Researchers have made great progress in understanding how certain mutations (changes) in DNA can cause normal cells to become cancerous. DNA is the chemical that carries the instructions for nearly everything our cells do. We usually look like our parents because they are the source of our DNA. However, DNA affects more than the way we look. Some genes (parts of our DNA) contain instructions for controlling when our cells grow and divide. Certain genes that promote cell division are called oncogenes. Others that slow down cell division, cause cells to die at the right time, or help repair DNA damage are called tumor suppressor genes. We know that DNA mutations (defects) that turn on oncogenes or turn off tumor suppressor genes can cause cancer.
Inherited genetic syndromes
Scientists have learned a lot about how certain genes you inherit from your parents can greatly increase your ovarian cancer risk. These include the BRCA1 and BRCA2 genes and several genes related to hereditary nonpolyposis colon cancer (see next section).
BRCA1 and BRCA2 genes
Inherited mutations in these genes were first found in women with breast cancer, and they are also responsible for most inherited ovarian cancers. When these genes are normal, they act as tumor suppressors -- they help prevent cancer by making proteins that keep cells from growing abnormally. But if you have inherited a mutation (defect) of one of these genes from either parent, this cancer-preventing protein is less effective, and your chances of developing breast and/or ovarian cancer increase. Mutations in BRCA1 and BRCA2 are about 10 times more common in those who are Ashkenazi Jewish than those in the general U.S. population.
The lifetime ovarian cancer risk for women with a BRCA1 mutation is estimated to be between 35% and 70%. This means that if 100 women had a BRCA1 mutation, between 35 and 70 of them would get ovarian cancer. For women with BRCA2 mutations the risk has been estimated to be between 10% and 30% by age 70. These mutations also increase the risks for primary peritoneal carcinoma and fallopian tube carcinoma.
In comparison, the ovarian cancer lifetime risk for the women in the general population is about 1.5%.
In this syndrome, people are primarily affected with thyroid problems, thyroid cancer, and breast cancer. Women also have an increased risk of ovarian cancer. It is caused by inherited mutations in the PTEN gene.
Hereditary nonpolyposis colon cancer
Women with this syndrome have a very high risk of colon cancer and also have an increased risk of developing cancer of the uterus (endometrial cancer) and ovarian cancer. Many different genes can cause this syndrome. They include MLH1, MLH3, MSH2, MSH6, TGFBR2, PMS1, and PMS2. An abnormal copy of any one of these genes reduces the body's ability to repair damage to its DNA. The lifetime risk of ovarian cancer in women with hereditary nonpolyposis colon cancer (HNPCC) is about 10%. This syndrome causes up to 1% of all ovarian epithelial cancers. An older name for HNPCC is Lynch syndrome.
People with this rare genetic syndrome develop polyps in the stomach and intestine while they are teenagers. They also have a high risk of cancer, particularly cancers of the digestive tract (esophagus, stomach, small intestine, colon). Women with this syndrome have an increased risk of ovarian cancer, including both epithelial ovarian cancer and a type of stromal tumor called sex cord tumor with annular tubules (SCTAT). This syndrome is caused by mutations in the gene STK11.
People with this syndrome develop polyps in the colon and small intestine and have a high risk of colon cancer. They are also more likely to develop other cancers, including cancers of the ovary and bladder. This syndrome is caused by mutations in the gene MUTYH.
Acquired genetic changes
Most DNA mutations related to ovarian cancer are not inherited but instead occur during a woman's life. In some cancers, acquired mutations of oncogenes and/or tumor suppressor genes may result from radiation or cancer-causing chemicals, but there is no evidence for this in ovarian cancer. So far, studies haven’t been able to specifically link any single chemical in the environment or in our diets to mutations that cause ovarian cancer. The cause of most acquired mutations remains unknown.
Most ovarian cancers have several acquired gene mutations. Research has suggested that tests to identify acquired changes of certain genes in ovarian cancers, like the p53 tumor suppressor gene or the HER2 oncogene, may help predict a woman's prognosis. The role of these tests is still not certain, and more research is needed.
Last Medical Review: 03/21/2013
Last Revised: 02/06/2014