Causes and Risk Factors of Ovarian Cancer

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Unlike some other cancers, it's not exactly known what causes ovarian cancer. However, hormonal, genetic, and lifestyle risk factors (including weight) may all play a role—likely in combination. Being aware of your personal risk may not only point you to changes you can make to reduce that risk but heighten the attention you give to any symptoms you may experience so that you can bring them up with your doctor as early as possible.

As you read on, it's important to remember the difference between correlation (a risk factor is associated with a disease) and causation (that risk factor brings about that disease). Having a risk factor for ovarian cancer does not mean that you will develop the disease, even if your risk is high. Likewise, many people who develop ovarian cancer do not have any of the known risk factors.

ovarian cancer risk factors
Illustration by Verywell

Common Risk Factors

Cancer begins after a series of mutations in the genetic material (DNA) of cancer cells leads them to grow in an out-of-control fashion, almost as if they're immortal. A number of theories about why this occurs have been proposed. 

Estrogen Therapy

This may increase or decrease the risk of ovarian cancer, depending on the type. Hormone replacement therapy (HRT) may increase your risk of ovarian cancer, but only if you take estrogen-only medications. Combined estrogen/progesterone HRT does not appear to raise the risk. 

Birth Control

Taking oral contraceptives (the Pill), in contrast, reduces your risk by up to 50 percent, with longer duration of use correlated with greater reduction. This risk reduction continues for at least 30 years after discontinuing the Pill. The birth control shot (Depo-Provera) is also associated with a lower risk.

Having a Child

Giving birth to a child before age 26 lowers your risk of developing ovarian cancer, as does breastfeeding. Having a first child over the age of 35, however, is linked with a slightly elevated risk.

Late Menopause

Late menopause is also associated with a higher risk. It could be that a greater number of ovulatory cycles plays a role in the development of these cancers. Ovulation does cause inflammation, and inflammation is associated with cancer, but the precise mechanism is still unknown.

Surgery

Tubal ligation surgery can significantly reduce the risk of ovarian cancer by up to 70 percent in some studies, though the mechanisms for this are unclear. Having a hysterectomy reduces the risk by around one-third. 

Endometriosis

Endometriosis, a condition in which uterine (endometrial) tissue grows outside of the uterus, is linked with a greater risk of ovarian cancer.

Infertility

It's not certain at this time if fertility drugs (such as Clomid) raise the risk of ovarian cancer, though a history of infertility is associated with a higher risk. Studies looking at fertility drugs and ovarian cancer did not see an increase in the risk of epithelial ovarian tumors, but rather the less common (and usually much less aggressive) stromal cell tumors.

Genetics

If you've watched the news and discussions about BRCA mutations, you probably realize that ovarian cancer can be hereditary. But in this day and age when gene testing is so new, it's important to talk about the difference between having a family history of cancer and having a known genetic mutation. Having a genetic predisposition to cancer does not mean that you will develop the disease, even if you carry a genetic mutation.

Family History

Many believe that testing positive for a BRCA mutation is necessary for the development of ovarian cancer, which is not the case. There are a number of genes that increase the risk of ovarian cancer, only one of which is the BRCA gene. It's also important to know that there are a few hundred different types of BRCA gene mutations, and the newly available do-it-yourself gene tests only check for a few of these.

If you have a family history of ovarian cancer (on either side of the family), your risk is increased. The risk is highest for those who have a first-degree relative who has had the disease, such as a mother, sister, or daughter. Having more than one relative with the disease raises the risk further. 

Here are other important facts to know in relation to your BRCA status:

  • If you are BRCA negative: You have a further increased risk of ovarian cancer if you have a relative (on either side of the family) who has or had ovarian cancer and a BRCA gene mutation. You also have an increased risk if you have a personal history of breast cancer.
  • If you are BRCA positive: Your risk of ovarian cancer is significantly higher than someone without the mutation. Roughly 40 percent of women with BRCA1 mutations and 20 percent of those with BRCA2 mutations are expected to develop ovarian cancer in their lifetime. Ovarian cancer in these individuals also tends to occur at an earlier age than it does in those without the mutation, and these cancers tend to be more aggressive as well.

If you suspect that BRCA gene mutations run in your family, talk to your doctor about who should have BRCA testing. If you are concerned, seeing a genetic counselor is important. A genetic counselor can look at patterns in the family, including the presence of other cancers that may be associated with an increased risk of ovarian cancer (such as breast cancer, colon cancer, pancreatic cancer, prostate cancer, and more). In fact, some people may be deemed to have a higher risk of ovarian cancer based on their family history of such cancers than those who have a known mutation.

Family Cancer Syndromes

Up to 10 percent of ovarian cancers are related to one of the cancer family syndromes in which a specific gene mutation is present. Many of these syndromes are related to mutations in what are known as tumor suppressor genes, which code for proteins that repair damaged DNA in cells. These include:

  • Lynch Syndrome (hereditary non-polyposis colon cancer ​or HNPCC): Women with HNPCC have roughly a 10 percent chance of developing ovarian cancer (along with a very high risk of developing colon cancer and a moderate risk of uterine cancer). There are several different genes that may be mutated in this syndrome.
  • Peutz-Jeghers Syndrome: This syndrome is related to mutations in the gene STK11 and is associated with an increased risk of ovarian cancer. It also is linked with the formation of colon polyps and an increased risk of several digestive tract cancers.
  • Cowden Disease: Also known as tumor hamartoma syndrome, this condition is related to a mutation in the PTEN gene. It increases the risk of benign tumors called hamartomas, as well as ovarian cancer, breast cancer, and thyroid cancer.

Height

Women who are tall (over 5 feet 8 inches) are more likely to develop ovarian cancer than shorter women. It's not known if this is related to height itself or the fact that height is tied to genetics that acts as a risk factor for ovarian cancer. 

Lifestyle Risk Factors

Lifestyle factors may play role in the development of ovarian cancer, and many of these (unlike your family history) can be modified or controlled.

Obesity

Obesity is linked to an increased risk of low-grade serous and invasive mucinous tumors (types of epithelial ovarian cancer) but does not appear to increase the risk of high-grade invasive serous cancers. Obesity also appears to be associated more with premenopausal than postmenopausal cancers.

There are several mechanisms that have been proposed. One is the increase in estrogen associated with obesity (fatty tissue produces androgens that are converted to estrogens). Obesity also often causes the body to have increased levels of insulin and insulin-like growth factor-1 (IGF-1) that may promote the development and growth of certain tumors. Furthermore, obesity increases inflammation, which has been associated with an increased risk of cancer.

Unfortunately, women who are obese or overweight are also at a greater risk of dying from ovarian cancer when present. Losing only five to 10 pounds may reduce your risk.

Talc Use

The use of feminine sprays and powders containing talc has been linked to ovarian cancer. Fortunately, it is fairly easy to eliminate this risk factor.

Diet

A few studies have found that a low-fat diet is associated with a lower risk of ovarian cancer, but there has been little evidence overall that diet plays a significant role.

Of interest, curcumin, a compound in the common curry ingredient turmeric, has been associated with a lower risk of ovarian cancer both in population studies and lab studies. Though more research is needed, if you like the spice, it can't hurt to incorporate it into your diet more often.

Smoking

Smoking is linked to one type of ovarian cancer: mucinous epithelial tumors. However, given the large number of cancers caused by smoking, quitting is a good idea.

Screening

There are no screening guidelines for this disease, primarily because screening has sadly not been found to reduce ovarian cancer-related deaths. Furthermore, such tests can lead to undesirable consequences, such as unnecessary surgery.

Some physicians may recommend twice yearly transvaginal ultrasounds and CA-125 blood tests (beginning at age 35 or whatever age is 10 years younger than when a relative was diagnosed) for those with a family history of ovarian or related cancers, or those with known mutations. However, this is not a unanimous practice for the same reasons. Removal of the tubes and ovaries (salpingo-oophorectomy) does reduce the risk of ovarian cancer by 75 percent to 90 percent.

This is all the more reason to be sure to bring any symptoms of ovarian cancer, even those that are subtle and vague, to the attention of your doctor. 

How Ovarian Cancer Is Diagnosed
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