Carcinogenesis Advance Access published online on August 27, 2007
Carcinogenesis, doi:10.1093/carcin/bgm190
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IGF-1 and IGFBP-3 gene variants influence on serum levels and prostate cancer risk in African Americans
Cancer Biology Program, Division of Biological Sciences, The University of Chicago, Chicago, IL (W.H., R.A.K.)
College of Medicine, Ohio State University Medical Center, Columbus, OH 43210 (C.G.)
Section of Genetic Medicine, Department of Medicine, Pritzker School of Medicine, The University of Chicago, Chicago, IL 60637 (W.H., E.R.S., R.A.K.)
Department of Clinical Pharmacology, University of Oxford, Oxford, OX2 6HA UK (C.B.)
Division of Urology, Howard University Hospital, Washington, DC 20060 (C.A.)
* Address for correspondence: Rick Kittles, Ph.D., Department of Medicine, Section of Genetic Medicine, The University of Chicago, 5841 South Maryland Avenue, MC6091, Chicago, IL 60637 USA, (773) 834-2271 office, (773) 702-2567 fax, rkittles{at}medicine.bsd.uchicago.edu
IGF-1 and IGFBP-3 are strong inhibitors of apoptosis and play a role in mediating the effects of growth hormone. Both IGF-1 and IGFBP-3 serum levels have been linked to cancer risk. Here we explore the relationship between three common IGF polymorphisms (C/T SNP (rs7965399) and a dinucleotide repeat (CA)n within the 5’ regulatory region of the IGF-1 gene and the -202 A/C SNP in the IGFBP-3 gene), serum levels and prostate cancer (Pca) risk in 767 African Americans enrolled in a clinic-based case-control study. IGF-1 and IGFBP-3 levels were measured using ICMA and the three polymorphisms were typed for 401 Pca cases and 366 age and ethnicity matched controls. Multiple linear regression and multivariable unconditional logistic regression were used to test for associations between genotypes and circulating IGF levels and Pca risk, respectively. The presence of at least one copy of the IGFBP-3 -202 C allele was strongly associated with lower IGFBP-3 serum levels (3,532ng/ml versus 3,106ng/ml; P=0.008). We also observed a two-fold increase in Pca risk for individuals homozygous for the IGFBP-3 -202 C allele (OR=2.4; 95%CI=1.2-4.8). Furthermore, IGF-1 (CA)19 genotypes were significantly associated with lower IGFBP-3 serum levels (P=0.003). Our results reveal that variation in the 5’-UTR of the IGF-1 and IGFBP-3 genes may be influencing IGF serum levels and Pca risk in African Americans and suggest a need to explore this variation across diverse populations. Our study adds clarity and further support to previous findings implicating serum IGFBP-3 levels and the IGFBP-3 -202A/C SNP in prostate carcinogenesis.
Received May 29, 2007; revised August 2, 2007; accepted August 14, 2007.
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