Variation in IGF1 gene may play a role in prostate cancer risk

Two variations in the gene for insulin-like growth factor I (IGF-1) are linked to an increased risk of prostate cancer, according to research performed by scientists from the Keck School of Medicine of the University of Southern California, the Broad Institute of Harvard and MIT, and the University of Hawaii.

"Our results suggest that inherited variation in IGF1 may play a role in prostate cancer risk," write the researchers in a paper published in the January 18, 2006, issue of the Journal of the National Cancer Institute.

USC scientists on this research team included: Iona Cheng, who was first author on the paper; Daniel Stram, Ph.D., professor of preventive medicine at the Keck School and the USC/Norris Comprehensive Cancer Center; Malcolm Pike, Ph.D., professor preventive medicine at the Keck School and USC/Norris; and Keck School of Medicine Dean Brian E. Henderson, M.D., who is also a distinguished professor in preventive medicine and neurology and the Kenneth T. Norris Jr. Chair in Cancer Prevention.

Cheng and her colleagues were able to tease out the relevant gene variations using data from the large Multiethnic Cohort study, for which Henderson is co-principal investigator. This population-based cohort study has collected data on more than 215,000 men and women from Los Angeles and Hawaii over the past decade.

From this cohort and information from cancer registries in California and Hawaii, the scientists were able to identify 2320 men who had developed prostate cancer and match them with 2290 men who did not have a prostate cancer diagnosis. This large population, the study's authors noted, provided "substantial [statistical] power to detect modest genetic effects."

The team knew that high circulating levels of IGF-1 had been linked by previous studies to an increase in prostate cancer risk, and so they focused on that gene and its single-nucleotide polymorphisms (SNPs): tiny point variations in the DNA code for a particular gene. What they found was that several SNPs across the gene were linked to an increased risk of prostate cancer, and two particular SNPs were identified that could account for the genetic associations they observed. Ten percent of the prostate cancer cases in this study could be explained by the variation in DNA sequence of these two polymorphisms.

Because of the ethnic diversity in the cohort's population--included in the group are African Americans, Hawaiians, Japanese Americans, Latinos and whites--the researchers were also able to look at the risk associated with the two SNPs across the five different ethnic groups. As it turned out, the increase in risk was the same throughout all the sub-groups, "suggesting that the inherited variation in IFG1 behaves similarly among ancestral groups and shares an overall biologic effect," the researchers observed.

"Our study critically evaluates the possibility of false positive results, and important issue faced by genetic association studies, and provides strong support for the involvement of the IGF pathway in the development of prostate cancer," Cheng noted. "By identifying the mechanisms in which inherited differences in IGF1 influence disease, we will further advance our understanding of prostate cancer biology and disease susceptibility."