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We don’t yet know exactly what causes most ovarian cancers. As discussed in Ovarian Cancer Risk Factors, 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.

The most recent and important finding about the cause of ovarian cancer is that it starts in cells at the tail ends of the fallopian tubes and not necessarily in the ovary itself. This new information may open more research studies looking at preventing and screening for this type of cancer. 

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.

Gene changes related to 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. Mutations in these genes can lead to the development of cancer.

Inherited genetic mutations

A small portion of ovarian cancers occur in women with inherited mutations linked to an increased risk of ovarian cancer. These include mutations in the BRCA1 and BRCA2 genes, as well as the genes related to other family cancer syndromes linked to an increased risk of ovarian cancer, such as PTEN (PTEN tumor hamartoma syndrome), STK11 (Peutz-Jeghers syndrome), MUTYH (MUTYH-associated polyposis, and the many genes that can cause hereditary nonpolyposis colon cancer (MLH1, MLH3, MSH2, MSH6, TGFBR2, PMS1, and PMS2).

Genetic tests can detect mutations associated with these inherited syndromes. If you have a family history of cancers linked to these syndromes, such as breast and ovarian cancers, thyroid and ovarian cancer, and/or colorectal and endometrial (uterine) cancer, you might want to ask your doctor about genetic counseling and testing. The American Cancer Society recommends discussing genetic testing with a qualified cancer genetics professional before any genetic testing is done. For more on this, see Genetics and Cancer.

Acquired genetic changes

Most mutations related to ovarian cancer are not inherited but instead occur during a woman's life and are called acquired mutations. In some cancers, these types of mutations leading to the development of cancer 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 mutations. Research has suggested that tests to identify acquired mutations in ovarian cancers, like the TP53 tumor suppressor gene or the HER2 oncogene, can help predict a woman's prognosis. The role of these tests is still not certain, and more research is needed.