Genetic variants of IGF1 associated with prostate cancer risk

Two common variants of IGF1, the gene that encodes insulin-like growth factor I are associated with an increased risk of developing prostate cancer, according to a report in the January 18, 2006 Journal of the National Cancer Institute.

“Currently, this set of IGF1 polymorphisms is being tested in the NCI-sponsored Breast and Prostate Cancer Consortium of Cohorts,” Dr. Matthew L. Freedman from Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, told Reuters Health. “If these SNPs remain positive in this larger sample set, we will have conclusive proof that men who possess these variants are at higher risk of developing prostate cancer.”Based on previous research showing a higher likelihood of developing advanced stage prostate cancer in men with higher levels of insulin-like growth factor I, Dr. Freedman and colleagues examined the genetic diversity of IGF1 in relation to prostate cancer risk among more than 4500 participants in the Multiethnic Cohort Study.Two haplotypes were significantly associated with prostate cancer risk, the authors report, and 2 perfectly correlated single nucleotide polymorphisms (SNPs) could accurately account for the haplotype findings.The CT genotype for SNP4 (rs7978742) was associated with a 25% higher prostate cancer risk than the TT genotype for SNP4, the results indicate. A similar association was shown for non-advanced disease (32% higher risk) and advanced disease (17% higher risk).”Approximately 10% of the cases of prostate cancer in this study could be attributed to carrying a SNP4 variant,” the investigators write.The associations appeared consistent across all racial and ethnic groups with the exception of Hawaiians, the researchers note.Further statistical testing indicated that a strong association similar to that observed with SNP4 would occur by chance only 5.6% of the time.”Prior evidence implicating the product of the IGF1 locus and prostate cancer pathogenesis, coupled with the results from this study, provide a solid foundation for attempting to replicate these findings in other cohorts, such as the National Cancer Institute-sponsored Cohort Consortium,” the authors conclude.”We are currently in the midst of evaluating whether these SNPs also influence insulin-like growth factor I levels in controls,” Dr. Freedman said. “We are only investigating this in men without prostate cancer as the state of having prostate cancer may in and of itself influence circulating insulin-like growth factor I levels.””We are entering a new era in human genetics,” Dr. Freedman added. “Much of the previous work in human genetics has focused on diseases that tend to be rare in the general population. Because of recent advances in a number of fields, we are now in a position to explore the genetic contributions to common clinical conditions.”(Source: J Natl Cancer Inst 2006;98:123-134: Reuters Health: Will Boggs, MD: Oncolink: February 2006.)