High IGF-I Levels Tied to Increased Prostate Cancer Risk

NEW ORLEANS--High concentrations of insulin-like growth factor I (IGF-I) in the circulation identify the men most at risk of prostate cancer as well as the women at highest risk of premenopausal breast cancer, according to results presented at the 89th annual meeting of the American Association for Cancer Research (AACR).

Michael Pollak, MD, Riesman Clinician-Scientist at Jewish General Hospital and professor of medicine and oncology at McGill University, Montreal, and his colleagues from Harvard performed a prospective case-control study using plasma samples from men in the Physicians’ Health Study.

Their subjects were 152 men who developed prostate cancer between the start of the study in 1982 and March 1992 and who also had a large enough plasma sample (taken in 1982) still left in 1997 to assay. The controls were 152 randomly selected subjects who did not get prostate cancer by March 1992.

Dr. Pollak and his co-workers found that prostate cancer patients averaged significantly higher IGF-1 levels than controls (269.4 ng/mL vs 248.9 ng/mL, P = 0.03). This relation held up even when the researchers accounted for weight, height, concentrations of various hormones, and other variables.

In a multivariate analysis, men in the highest quartile for IGF-I had a relative risk of 4.32, compared with the men in the lowest quartile. These results were published in a recent issue of Science (January 23, 1998).

Men With Low PSA

When the investigators focused on men with prostate-specific antigen (PSA) values less than 4 ng/mL, they found that the risk of prostate cancer again increased as the IGF-I value rose, suggesting that IGF-I levels could help predict risk in men with low PSA values.

"We regard this as a very interesting but early result," Dr. Pollak said. If confirmed, he believes that it could be helpful in several ways.

First, testing men for IGF-I as well as PSA may give a fuller picture of their risk of prostate cancer. Second, it is possible that IGF-I concentrations in men who already have prostate cancer might identify those men whose cancer is most likely to progress and who need the closest monitoring. Third, these results suggest that investigators should look into the possibility of developing anti-IGF-I agents as treatments for prostate cancer in men with high IGF-I values.

Susan Hankinson, PhD, of the Nurses’ Health Study, and Dr. Pollak have recently linked high IGF-I concentrations and the risk of breast cancer in premenopausal women. As in the prostate cancer study, women with the highest IGF-I values have about four times the risk of breast cancer, compared to women with lower values. The increased risk appears to apply only to premenopausal women. This work appeared in The Lancet of May 9, 1998, he said.

"While the risk associated with high IGF-1 levels is much less than that associated with mutations in cancer-causing genes, such as BRCA1, the burden of cancer related to high IGF-1 levels may be considerable," Dr. Pollak said. "The reason is that high IGF-1 levels are much more common than mutations in BRCA1 or other similar genes."