Hormone Linked to Higher Risk of Ovarian Cancer

By Merritt McKinney

NEW YORK Oct 29, 2002 (Reuters Health) - High levels of a protein called insulin-like growth factor (IGF)-I may increase women"s risk of developing ovarian cancer before age 55, the results of a new study suggest.

Measuring IGF-I levels is unlikely to be useful as a screening test for ovarian cancer, according to the study"s lead author, Dr. Rudolf Kaaks, of the International Agency for Research on Cancer in Lyon, France. However, he told Reuters Health that the discovery of elevated levels of the growth factor in women with ovarian cancer raises the possibility that diet, which can increase IGF-I, may be involved in ovarian cancer.

Ovarian cancer is highly treatable in its early stages, but the cancer is rarely caught early, in part because its symptoms, such as bloating and abdominal discomfort, can signal any number of problems. Also, there is not a good screening test for ovarian cancer, so more than two thirds of cases are not detected until after cancer has spread outside the ovaries. Once ovarian cancer spreads, the 5-year-survival rate is only 29%.

Because detecting ovarian cancer before it spreads can be life-saving, the scientific search is on for ways to detect the disease. Some preliminary studies have found that IGF-I levels are higher than normal in ovarian tumors, and there is some evidence that IGFBP-3, a protein that transports IGF-I, is reduced in ovarian cancer.

In the new study, Kaaks and his colleagues tested the connection between IGF-I, IGFBP-3 and ovarian cancer in women enrolled in several long-term health studies. The study included 132 women with ovarian cancer and 263 healthy women who were matched by age.

Based on blood samples taken at least one year before women were diagnosed with cancer, the researchers did not detect any overall link between levels of IGF-I or IGFBP-3 and ovarian cancer. However, for women who received a cancer diagnosis before age 55, levels of IGF-I but not IGFBP-3 seemed to affect cancer risk. Among the younger women, those with the highest levels of IGF-I were almost five times more likely to be diagnosed with ovarian cancer than women with the lowest levels.

The study did not examine how IGF-I may increase the risk of ovarian cancer, but the investigators suggest several possibilities in their report in the International Journal of Cancer. The growth factor could promote tumor growth by increasing the proliferation of cells, as well as by inhibiting the mechanism that instructs defective cells to kill themselves. Another possibility, according to the report, is that IGF-I may somehow interact with hormones or ovulation in premenopausal women.

"I doubt whether elevated IGF-I would ever be useful as a marker for ovarian cancer screening," Kaaks told Reuters Health. It is "unlikely," he said, that high levels of IGF-I would be caused by a preclinical ovarian tumor.

"Rather, we think that elevated IGF-I levels are due to other causes preceding ovarian cancer development," he said.

He explained that many factors, including nutrition, affect blood levels of IGF-I. "It is possible," Kaaks said, "that the elevated IGF-I in women at increased risk of ovarian cancer was a result of nutritional factors."

According to Kaaks, "Circulating IGF-I might thus provide a physiologic link between a Western lifestyle, characterized amongst other things by a diet rich in energy and animal protein, and ovarian cancer risk." He noted that the risk of ovarian cancer is much higher in industrially developed countries than in developing nations.

SOURCE:

• International Journal of Cancer 2002;101:549-554.