Causes & Risk Factors of Ovarian Cancers

Ovarian cancer includes several different diseases that can develop in the ovaries. Closely related cancers can also begin in the fallopian tubes or the primary peritoneum, the thin layer of tissue lining the abdomen and covering many of its organs.

Although ovarian cancer was once thought to begin primarily on the surface of an ovary, research has changed how physicians understand the most common epithelial subtype. Many high-grade serous cancers are now believed to begin as abnormal cells near the fimbriae, the outer ends of the fallopian tubes. These cells may later spread to the ovaries or peritoneal surfaces, where larger tumors become detectable.

Ovarian cancer may not cause noticeable symptoms in its early stages. Understanding the factors that influence risk can help patients determine whether they may benefit from genetic counseling, individualized risk assessment, or preventive care.

What Causes Ovarian Cancer?

Ovarian cancer develops when genetic changes cause cells in the ovary, fallopian tube, or peritoneum to grow and divide without normal controls. Healthy cells follow genetic instructions that regulate their growth, function, repair, and natural death. When important genes become altered, abnormal cells may continue multiplying and eventually form a tumor.

The precise sequence leading to cancer varies among ovarian cancer subtypes. Some genetic changes are inherited from a parent, while others develop within cells during a person’s lifetime.

As we've understood more about the biology of ovarian cancer and we've taken care of more individuals who are otherwise healthy, we are developing more patient-centered options for prevention.

Karen Lu, MD

Inherited Genetic Mutations

Approximately 10% to 15% of ovarian cancers are hereditary. An inherited harmful genetic change is present throughout the body and can be passed from either parent. Having one of these changes does not mean cancer is certain to develop, but it may raise lifetime risk enough to affect screening, prevention, and treatment decisions.

• BRCA1 and BRCA2 mutations: BRCA1 and BRCA2 are tumor-suppressor genes that help repair damaged DNA. Harmful inherited changes can interfere with this protective function. Current estimates suggest that approximately 39% to 58% of women with a harmful BRCA1 change and 13% to 29% of women with a harmful BRCA2 change will develop ovarian, fallopian tube, or primary peritoneal cancer during their lifetime.
• Lynch syndrome: Lynch syndrome is caused by inherited changes involving DNA mismatch-repair genes such as MLH1, MSH2, MSH6, PMS2, or EPCAM. It is associated with an increased risk of colorectal, endometrial, ovarian, and several other cancers. Ovarian cancer risk varies according to the specific gene involved and the person’s family history.
• Other hereditary genes: Harmful inherited changes involving genes such as BRIP1, RAD51C, and RAD51D can also increase ovarian cancer risk. Multigene testing may identify additional variants that influence an individual’s risk-management recommendations.

Acquired Genetic Changes

Most ovarian cancers are not caused by an inherited mutation. Instead, genetic changes develop within individual cells during a person’s lifetime. These acquired, or somatic, changes are present in the tumor rather than throughout the body and cannot be passed to children.

The processes that lead to acquired mutations are complex and differ among cancer subtypes. They may involve age-related cellular changes, chronic inflammation, hormonal or reproductive influences, and precursor lesions in the fallopian tubes. Researchers continue to study how these factors interact and why ovarian cancer develops in some people but not others.

Risk Factors for Ovarian Cancer

A risk factor is something associated with a greater likelihood of developing a disease. Having one or more ovarian cancer risk factors does not mean that cancer will occur. Likewise, someone without an obvious risk factor can still be diagnosed.

Modifiable Risk Factors (Factors You Can Control)

These factors may be influenced through medical decisions or lifestyle changes, although they are only part of a person’s overall risk profile.

• Menopausal hormone therapy: Systemic menopausal hormone therapy has been associated with a small increase in ovarian cancer risk. The association appears stronger with estrogen-only treatment and longer use, although the individual risks and benefits depend on the specific medication, treatment duration, and patient’s medical history.
• Higher body weight: Obesity is associated with an increased risk of some ovarian cancer subtypes. The strength of the relationship varies according to tumor type and other individual health factors.
• Tobacco use: Smoking is associated with an increased risk of mucinous ovarian cancer, which is a relatively uncommon subtype. It has not been shown to raise the risk of every form of ovarian cancer.

Patients should not stop hormone therapy, contraception, or another prescribed treatment solely because of general cancer-risk information. Personal decisions should be discussed with a qualified health care professional.

Non-Modifiable Risk Factors (Factors You Cannot Change)

These factors generally cannot be changed, but recognizing them may help identify patients who could benefit from genetic counseling or more individualized prevention discussions.

• Older age: Ovarian cancer can occur at any age, but the likelihood increases over time. Most epithelial ovarian cancers are diagnosed after menopause.
• Inherited genetic syndromes: Harmful changes in BRCA1, BRCA2, Lynch syndrome genes, BRIP1, RAD51C, RAD51D, and other cancer-susceptibility genes can significantly increase ovarian cancer risk. Genetic counseling can help patients understand whether testing may be appropriate and what the results could mean for them and their relatives.
• Family history: Having a first-degree relative, such as a mother, sister, or daughter, with ovarian, fallopian tube, or primary peritoneal cancer increases risk, even when genetic testing does not identify a known inherited mutation. A pattern of ovarian, breast, pancreatic, prostate, colorectal, or endometrial cancers on either side of the family may also suggest an inherited cancer syndrome.
• Reproductive history: Never having given birth and having fewer pregnancies are associated with a higher ovarian cancer risk. Earlier menstruation and later menopause have also been studied because they may result in a greater number of lifetime ovulatory cycles, although these associations can vary among ovarian cancer subtypes.
• Endometriosis: Endometriosis occurs when tissue similar to the uterine lining grows outside the uterus. It is associated with an increased risk of certain ovarian cancer subtypes, particularly clear cell and endometrioid carcinomas.

"I hope to provide other young adults with cancer with the support and encouragement that I received during a very difficult time in my life."

Renee, Ovarian Cancer Survivor

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Can Ovarian Cancer Be Prevented?

Not every case of ovarian cancer can be prevented. However, several reproductive, medical, and surgical factors are associated with a lower risk. The most appropriate approach depends on a person’s inherited genetic results, family history, age, overall health, reproductive plans, and personal preferences.

Oral Contraceptives

Use of oral contraceptives is associated with an approximately 30% to 50% reduction in ovarian cancer risk, with greater protection generally seen after longer use. The protective association can continue for many years after the pills are discontinued and has also been observed among people with harmful BRCA1 or BRCA2 changes.

Oral contraceptives also have possible side effects and are not appropriate for everyone. Patients should discuss their personal and family medical histories with a health care professional rather than starting birth control solely to reduce cancer risk.

Pregnancy and Breastfeeding

Giving birth and breastfeeding are associated with a lower risk of ovarian cancer. The reduction generally increases with additional full-term pregnancies and longer cumulative breastfeeding duration. These factors may reduce the number of lifetime ovulatory cycles, although ovarian cancer risk is influenced by several biological processes.

Risk-Reducing Salpingo-Oophorectomy

People with certain inherited genetic changes may be advised to consider surgical removal of both fallopian tubes and ovaries after completing childbearing. This procedure is known as a risk-reducing bilateral salpingo-oophorectomy.

For people with harmful BRCA1 or BRCA2 changes, this surgery substantially reduces the risk of ovarian, fallopian tube, and primary peritoneal cancers and has been associated with improved survival. It does not eliminate risk completely because primary peritoneal cancer can still develop after the ovaries and fallopian tubes have been removed.

The recommended timing differs according to the gene involved, family history, age, reproductive plans, and the potential effects of surgical menopause. These decisions should be made with input from a genetic counselor and a gynecologic oncology specialist.

Opportunistic Salpingectomy

For average-risk patients who are already undergoing pelvic surgery for another medical reason, removing the fallopian tubes while retaining healthy ovaries may help lower future ovarian cancer risk. This is called opportunistic salpingectomy.

It may be discussed during procedures such as hysterectomy or permanent sterilization. Retaining the ovaries avoids the immediate surgical menopause caused by removing both ovaries, but salpingectomy does not eliminate the possibility of ovarian or primary peritoneal cancer.

Healthy Lifestyle Decisions

No diet, supplement, or exercise program has been proven to prevent ovarian cancer. Still, maintaining a healthy weight and avoiding tobacco can support overall health and may reduce risks associated with obesity and mucinous ovarian cancer. Patients should be cautious about products marketed specifically as ovarian cancer prevention supplements because these claims may not be supported by reliable evidence.

Common Questions About Ovarian Cancer Causes and Risk Factors

Take a closer look at ovarian cancer causes and risk factors by browsing some frequently asked questions on this topic:

• What can I do to decrease my risk of ovarian cancer?
• What’s the No. 1 risk factor for ovarian cancer?
• Is there a genetic predisposition for ovarian cancer?
• Is there a connection between breast cancer and ovarian cancer?

Get the Ovarian Cancer Help You Need at Moffitt Cancer Center

The multispecialty team at Moffitt Cancer Center’s gynecological clinic is committed to conducting groundbreaking clinical trials and delivering highly individualized care to better prevent, diagnose and treat ovarian cancer. This patient-first focus ensures we remain firmly positioned at the forefront of cancer treatment. In recognition of our research efforts, the National Cancer Institute has designated Moffitt as the only Comprehensive Cancer Center based in Florida, and national experts consistently rank Moffitt among the top 1% of cancer centers in the U.S.

To discuss your ovarian cancer risk factors, consult with a genetic counselor or learn more about Moffitt’s ovarian cancer treatment options, call 1-888-663-3488 or complete a new patient registration form online. A referral isn’t necessary to visit Moffitt, and you’ll be matched with the right clinician for your needs as soon as possible.

References

Ovarian Cancer Risk Factors
What Are the Risk Factors for Ovarian Cancer? | CDC
How to Prevent Ovarian Cancer | Oral Contraceptives & Ovarian Cancer | American Cancer Society