Anti-Inflammatory Drugs May Lower Ovarian Cancer Risk

Research Still In Early Stages

 < March 31, 2004 > -- Scientists say they have uncovered a critical clue about why pain medications, such as aspirin, ibuprofen, Celebrex^TM, and Vioxx^TM,   may help prevent ovarian cancer.

These popular anti-inflammatory medications inhibit the cox-2 enzyme. Apparently, they also slow the rapid turnover of cells within the ovary and reduce the risk for potentially malignant cells, according to a study presented at the American Association for Cancer Research annual meeting.

Ovarian cancer is the fifth leading cancer killer of women in the US, claiming nearly 15,000 lives per year. The disease, while relatively uncommon, has an especially high fatality rate because ovarian tumors tend to escape detection until the cancer has already spread to other organs.

Cox-2 is best known for its role in triggering inflammatory responses that, if misdirected, can lead to headache or arthritic pain.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen block both cox-1 and cox-2 enzymes, while the new arthritis medications Celebrex^TM and Vioxx^TM relieve pain by reducing the expression of cox-2 only. 

The cox-1 enzyme also protects the stomach lining, and because Celebrex^TM and Vioxx^TM do not inhibit it, they are prescribed to people with gastrointestinal problems.

The US Food and Drug Administration (FDA) has approved the new arthritis medications for the prevention of colon cancer, and studies have suggested the drugs might help reduce a woman's chances of breast cancer.

Researchers Take Study to Ovarian Cancer

The new study, led by Dr. Xiang-Xi Xu at Fox Chase Cancer Center, focused on what the researchers knew to be the prime tumor site within an ovary.

"Ninety percent of cancers, including ovarian cancer, come from the layer of cells on the surface of tissue, called epithelial cells," Dr. Xu explains.

Epithelial cells are typically organized side by side in a collagen "grid" called the basement membrane. While examining ovarian epithelial cells in the lab, the researchers discovered that overexpression of the cox-2 enzyme can seriously damage the membrane.

According to Dr. Xu, destruction of the basement membrane has a negative impact on the life cycle of epithelial cells.

"The basement membrane not only organizes them but it gives them signals, too," he explains, keeping normal, healthy cells alive while weeding out mutated cells.

Cox-2 destruction of the basement membrane "speeds up the accumulation of mutant or precursor cells, increasing the chances of getting cancer," Dr. Xu says.

Dr. Xu now believes cox-2 inhibitors may help prevent ovarian cancer by reducing the enzyme's destruction of the basement membrane.

He also notes that "cox-2, besides inflammation, has other functions in our body, including [stimulation of] ovulation."

"Every time you ovulate, you have to get rid of the basement membrane," Dr. Xu says, and "it's known that the more a woman ovulates, the more her chances of getting ovarian cancer."

Indeed, women who have fewer ovulations over a lifetime due to pregnancy, breast-feeding, or use of birth control pills appear to be at lowered risk for ovarian cancer.

The bottom line, according to Dr. Xu, is any drug that lowers the activity of cox-2 might reduce ovarian cancer risk.

Research Promising, But In Early Stages

Dr. Debbie Saslow, director for breast and gynecologic cancers at the American Cancer Society, says the findings provide "new information" on the mechanisms behind ovarian tumors, but cautions "this is still in the basic research stage."

To further this research, Dr. Xu's team plans a population-based study looking at tissue changes in the ovaries of women at especially high risk for ovarian cancer due to a family history of the disease.

Comparing tissues collected from NSAID users and nonusers, "we will look at the ovary to see if there are any structural changes - indicators of either disease or some positive effect of the compounds," Dr. Xu says.

Dr. Saslow says the real "hot topic" in ovarian cancer research these days is the race for an effective early-detection test, with various screening technologies already winding their way through the FDA approvals process.

While it is too early to hope that any one test will be prove effective, "there's been a lot of interest there," she says.

Always consult your physician for more information.

Online Resources

American Cancer Society

Centers for Disease Control and Prevention (CDC)

HealthierUS.Gov

National Cancer Institute

National Institutes of Health (NIH)

National Library of Medicine

National Ovarian Cancer Coalition

US Food and Drug Administration

Find a Physician at
St. John's Mercy or call our Physician Referral Service at 314-FOR-DOCS. 

For more information on Ovarian Cancer, please visit health information modules on this Web site.

Ovarian Cancer FAQ

Ovarian cancer is a disease in which malignant cells are found in an ovary. There are three types of ovarian tumors, named for the tissue in which they are found:

• epithelial cell - cells that cover the surface of the ovary. Most of these tumors are benign (noncancerous). However, epithelial ovarian cancer accounts for 85 percent to 90 percent of ovarian cancer cases.
  
  
• germ cell - cells that form the eggs in the ovary.
  
  
• stromal cell - cells that form the ovary and produce female hormones.

The cause of ovarian cancer is unknown, but there are certain risk factors that indicate an increase in a woman's chance of developing ovarian cancer.

The following have been suggested as risk factors for ovarian cancer:

• early menarche - starting monthly periods early - before the age of 12
  
  
• late menopause (after the age of 52)
  
  
• age-over the age of 50
  
  
• hormone replacement therapy
  Some studies have suggested that women who use hormone replacement therapy after menopause may have a slightly increased risk of ovarian cancer. 
  
  
• infertility (inability to become pregnant)
  
  
• having a first child after the age of 30
  
  
• personal history of breast or colon cancer
  
  
• family history
  First-degree relatives (such as mother, daughter, sister) of a woman who has had ovarian cancer are at a risk for developing the disease. The risk increases if two or more first-degree relatives have had ovarian cancer. A family history of breast or colon cancer is also associated with an increased risk of developing ovarian cancer. 
  
  
• fertility drugs

Suggested preventive measures include the following:

• healthy diet (high in fruits, vegetables, grains, and low in saturated fat)
  
  
• birth control pills
  
  
• pregnancy and breastfeeding 
  
  
• hysterectomy - surgical removal of the uterus.
  
  
• tubal ligation - surgery to block the fallopian tubes to prevent conception.
  
  
• oophorectomy - surgical removal of ovaries.
  

Research studies have shown that certain genes are responsible for increasing the risk of ovarian and breast cancer.

According to the National Cancer Institute, about 5 percent to 10 percent of breast and ovarian cancers are due to known predisposing genetic factors. This means that the majority of breast and ovarian cancers are, in fact, not inherited.

Always consult your physician for more information.