The discovery that two variations in the gene for insulin-like growth factor I (IGF-I) are linked to increased risk for prostate cancer in multiple racial and ethnic groups may improve risk stratification for individuals, according to an article in the January 18 issue of the Journal of the National Cancer Institute.

“Our results suggest that inherited variation in IGF-I may play a role in prostate cancer risk,” wrote the researchers, led by Dr. Iona Cheng.

Cheng and colleagues from several American universities were able to tease out the relevant gene variations using data from the large Multiethnic Cohort study, for which coauthor Brian Henderson is co-principal investigator.

The population-based cohort study has collected data on more than 215,000 men and women from Los Angeles, California and Hawaii over the past decade. From this cohort and information from cancer registries, 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. The large size of the total population, the study’s authors noted, provided “substantial [statistical] power to detect modest genetic effects.”

The team knew that high circulating levels of the growth factor had been linked by previous studies to an increase in prostate cancer risk, so they focused on that gene and its single-nucleotide polymorphisms (SNPs).

They found that several single-nucleotide variations across the gene were linked to an increased risk of prostate cancer, and two particular variations were identified that could account for the genetic associations they observed. Ten percent of the prostate cancer cases in the study could be explained by the variation in DNA sequence of the two polymorphisms.

Because of the ethnic diversity in the cohort’s population?including African Americans, Hawaiians, Japanese Americans, Latinos and whites?the researchers were also able to look at the risk associated with the two variations across the five different ethnic groups. The increase in risk was the same throughout all subgroups, “suggesting that the inherited variation in IFG-1 behaves similarly among ancestral groups and shares an overall biologic effect,” the researchers observed.

“Our study critically evaluates the possibility of false positive results, an 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 IGF-1 influence disease, we will further advance our understanding of prostate cancer biology and disease susceptibility.”