IGF-1 gene may raise prostate cancer risk

San Francisco-A prospective analysis of more than 4,600 men indicates that the insulin-like growth factor (IGF-1) gene appears to play a role in prostate cancer development and carcinogenesis, according to a recently published study (J Natl Cancer Inst 2006; 98:123-34).

However, the study found that genetic differences do not seem to account for the noteworthy variance in prostate cancer among ethnic groups.

"We found several polymorphisms across the gene that were associated with a higher risk of prostate cancer, but there were two single nucleotide polymorphisms [SNPs] in particular that could account for the genetic effects observed," said first author Iona Cheng, PhD, MPH, a postdoctoral fellow in the department of epidemiology and biostatistics, University of California at San Francisco.

"Prostate cancer displays dramatic differences in risk across ethnic groups. African-American men have the highest risk, while Asian men have the lowest," Dr. Cheng said. "But it doesn't seem that genetic differences in IGF-1 explain the differences in risk of disease across different ethnic groups."

The Multiethnic Cohort study was the first comprehensive effort to look at the role of the gene in prostate cancer, Dr. Cheng said. A previous large study of 530 patients with prostate cancer, in the Physician's Health Study conducted by Harvard University researchers, found that higher levels of IGF-1 in a patient's circulatory system were associated with prostate cancer.

"The Multiethnic Cohort is a unique cohort that allows us to study a large number of diverse ethnic groups," he said.

The mitogen IGF-1 has been associated with other forms of cancer. The protein promotes cell growth and inhibits cell death.

"The protein itself binds to the IGF receptor, which will then transmit a signal that will stimulate downstream effects, causing a cell to replicate," Dr. Cheng explained. "The next step we're working toward is to understand whether this genetic variation influences the amount of IGF-1 protein in the circulatory system."

To confirm the study's findings, the analysis will be repeated among individuals grouped in the National Institutes of Health's Breast-Prostate Cohort Consortium, which includes the American Cancer Society, the European Prospective Investigation into Cancer and Nutrition, the Harvard Cohort, the Multiethnic Cohort, the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, and the Alpha Tocopherol Beta Carotene Cancer Prevention Study, said Dr. Cheng, who will participate in the analysis with the consortium.

"In contrast to BRCA-1 and -2 mutations and breast cancer, in which a very small percentage of the population, such as 1% or 2%, are carriers of the mutation with a high risk of disease, the genetic variation we examined in IGF-1 is more common in the population, but with a more modest risk of disease," Dr. Cheng said.

The study indicated that about 10% of prostate cancer cases could be attributed to the genetic polymorphisms, she added, noting that patients in the control group, who did not have prostate cancer, also exhibited the IGF polymorphism.