| Literature DB >> 20484221 |
Fredrick R Schumacher1, Iona Cheng, Matthew L Freedman, Lorelei Mucci, Naomi E Allen, Michael N Pollak, Richard B Hayes, Daniel O Stram, Federico Canzian, Brian E Henderson, David J Hunter, Jarmo Virtamo, Jonas Manjer, J Michael Gaziano, Laurence N Kolonel, Anne Tjønneland, Demetrius Albanes, Eugenia E Calle, Edward Giovannucci, E David Crawford, Christopher A Haiman, Peter Kraft, Walter C Willett, Michael J Thun, Loïc Le Marchand, Rudolf Kaaks, Heather Spencer Feigelson, H Bas Bueno-de-Mesquita, Domenico Palli, Elio Riboli, Eiliv Lund, Pilar Amiano, Gerald Andriole, Alison M Dunning, Dimitrios Trichopoulos, Meir J Stampfer, Timothy J Key, Jing Ma.
Abstract
The insulin-like growth factor (IGF) pathway has been implicated in prostate development and carcinogenesis. We conducted a comprehensive analysis, utilizing a resequencing and tagging single-nucleotide polymorphism (SNP) approach, between common genetic variation in the IGF1, IGF binding protein (BP) 1, and IGFBP3 genes with IGF-I and IGFBP-3 blood levels, and prostate cancer (PCa) risk, among Caucasians in the NCI Breast and Prostate Cancer Cohort Consortium. We genotyped 14 IGF1 SNPs and 16 IGFBP1/IGFBP3 SNPs to capture common [minor allele frequency (MAF) >or= 5%] variation among Caucasians. For each SNP, we assessed the geometric mean difference in IGF blood levels (N = 5684) across genotypes and the association with PCa risk (6012 PCa cases/6641 controls). We present two-sided statistical tests and correct for multiple comparisons. A non-synonymous IGFBP3 SNP in exon 1, rs2854746 (Gly32Ala), was associated with IGFBP-3 blood levels (P(adj) = 8.8 x 10(-43)) after adjusting for the previously established IGFBP3 promoter polymorphism A-202C (rs2854744); IGFBP-3 blood levels were 6.3% higher for each minor allele. For IGF1 SNP rs4764695, the risk estimates among heterozygotes was 1.01 (99% CI: 0.90-1.14) and 1.20 (99% CI: 1.06-1.37) for variant homozygotes with overall PCa risk. The corrected allelic P-value was 8.7 x 10(-3). IGF-I levels were significantly associated with PCa risk (P(trend) = 0.02) with a 21% increase of PCa risk when compared with the highest quartile to the lowest quartile. We have identified SNPs significantly associated with IGFBP-3 blood levels, but none of these alter PCa risk; however, a novel IGF1 SNP, not associated with IGF-I blood levels, shows preliminary evidence for association with PCa risk among Caucasians.Entities:
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Year: 2010 PMID： 20484221 PMCID： PMC2901143 DOI： 10.1093/hmg/ddq210
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150