Variations in growth-factor gene linked to risk of prostate cancer


Researchers from the Keck School of Medicine of the University of Southern California, the Broad Institute of Harvard and MIT, and the University of Hawaii, found that two variations in the gene for insulin-like growth factor I ( IGF-1 ) are linked to an increased risk of prostate cancer.

" 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 Journal of the National Cancer Institute.

Researchers were able to tease out the relevant gene variations using data from the large Multiethnic Cohort study.
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 researchers 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 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 ).
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."

Source: University of Southern California, 2006


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