Originally created 07/03/97

Researchers find link between menstrual cycles, ovarian cancer



WASHINGTON - Bearing children and taking birth control pills can lower the risk of ovarian cancer by reducing the lifetime number of ovulations, or menstrual cycles, experienced by a woman, according to a study published today.

Dr. Andrew Berchuck, professor of gynecologic oncology at Duke University Medical Center in Durham, N.C., said the research found that a high number of ovulations - more than 376 in a lifetime, - can increase by nine times the chances of producing cells with a genetic flaw linked to ovarian cancer.

A statistical link between ovulations and ovarian cancer has been known for some time, but the new study suggests the reason: A high number of ovulations increases the chances a tumor suppressor gene called p53 can be mutated, Berchuck said.

"We show that in women with ovarian cancer there is a very strong association between having a lot of ovulatory cycles and an alteration in the p53 gene," he said. "The majority of ovarian cancers have this p53 mutation and these mutations occur because of ovulation."

Anything that lowers the number of lifetime ovulation cycles thus reduces the risk of ovarian cancer, Berchuck said.

"If you have one baby, it decreases your risk by about 13 percent," he said. "If you have three babies, your risk is about half that of women who had no babies."

The study also clearly shows that birth control pills, which control ovulation, protect against ovarian cancer, he said. If the pill is taken for a year, it gives a 10 percent protection, while its use for five to 10 years cuts the risk in half.

Nursing a newborn also reduces the number of ovulations.

The study appears today in the Journal of the National Cancer Institute. In an editorial, Dr. Alice S. Whittemore and Dr. Valerie McGuire of the Stanford University School of Medicine note the information could create new research possibilities about a deadly cancer that is still poorly understood.

Ovarian cancer is diagnosed in about 27,000 American women annually, most of them near age 60. About 15,000 women die of the disease every year.

The disease is only one-sixth as common as breast cancer, but it is far more lethal. Only about 30 percent of ovarian cancer patients survive five years, compared to about 70 percent of breast cancer patients.

No reliable screening test exists, Berchuck noted. As a result, the disease is usually discovered after it has spread beyond the ovaries, when treatment is much less successful.

Berchuck's study supports the theory that the p53 gene may mutate as a result of an increase in cell growth that occurs with a high number of lifetime ovulations. With each ovulation, there is a rupture of epithelium tissue, which leads to a growth of new cells. Each time a new cell is produced, there is a risk of a genetic mistake, such as a p53 mutation.

Thus, the more cell proliferations that occur, the higher the cancer risk.

Berchuck noted, however, that p53 mutations account for only two-thirds of ovarian cancers. That means there is a "subset" of such cancers that may be caused by other factors.

In the study, Berchuck and associates studied the menstrual history of 3,363 women who were cancer free and 197 cancer patients. They also tested for p53 mutations.

They then calculated the number of ovulation cycles for each woman, based on the age at which her periods started and stopped. The formula counted 13 cycles a year. Since the average age for starting ovulation is 12.5 years and for menopause is 50, a typical lifetime of ovulations would number 487.

From this, the study subtracted months spent pregnant, breast-feeding or using birth control pills to arrive at an individual ovulation history.

A "medium" ovulation history was 235 to 375 cycles, while a "high" history was 376 to 533.

The researchers then compared the number of cycles among cancer patients who had mutated p53 genes and those whose tumors had no such mutation. They found that those with a "high" number of cycles were seven times more likely to have the mutated genes.

When compared to the cancer-free group, women with "high" ovulation histories were nine times more likely to have the mutated gene. Women with a "medium" number of cycles were about 4.3 times more likely.