@article{3089519,
    title = "A comprehensive analysis of common IGF1, IGFBP1 and IGFBP3 genetic variation with prospective IGF-I and IGFBP-3 blood levels and prostate cancer risk among Caucasians",
    author = "Schumacher, F.R. and Cheng, I. and Freedman, M.L. and Mucci, L. and Allen, N.E. and Pollak, M.N. and Hayes, R.B. and Stram, D.O. and Canzian, F. and Henderson, B.E. and Hunter, D.J. and Virtamo, J. and Manjer, J. and Gaziano, J.M. and Kolone, L.N. and Tjønneland, A. and Albanes, D. and Calle, E.E. and Giovannucci, E. and David Crawford, E. and Haiman, C.A. and Kraft, P. and Willett, W.C. and Thun, M.J. and Le Marchand, L. and Kaaks, R. and Feigelson, H.S. and Bueno-de-Mesquita, H.B. and Palli, D. and Riboli, E. and Lund, E. and Amiano, P. and Andriole, G. and Dunning, A.M. and Trichopoulos, D. and Stampfer, M.J. and Key, T.J. and Ma, J.",
    journal = "Human Molecular Genetics",
    year = "2010",
    volume = "19",
    number = "15",
    pages = "3089-3101",
    issn = "0964-6906, 1460-2083",
    doi = "10.1093/hmg/ddq210",
    keywords = "somatomedin binding protein 1;  somatomedin binding protein 3;  somatomedin C;  somatomedin binding protein 1;  somatomedin binding protein 3;  somatomedin C, adult;  article;  blood analysis;  cancer risk;  carcinogenesis;  Caucasian;  gene frequency;  gene identification;  gene sequence;  genetic association;  genetic polymorphism;  genetic risk;  genetic variability;  genotype;  heterozygote;  homozygote;  human;  human tissue;  major clinical study;  male;  priority journal;  promoter region;  prostate cancer;  single nucleotide polymorphism;  statistical analysis;  aged;  blood;  breast tumor;  Caucasian;  cohort analysis;  female;  gene linkage disequilibrium;  genetic predisposition;  genetic variability;  genetics;  metabolism;  middle aged;  prostate tumor;  risk factor, Aged;  Breast Neoplasms;  Cohort Studies;  European Continental Ancestry Group;  Female;  Genetic Predisposition to Disease;  Genetic Variation;  Humans;  Insulin-Like Growth Factor Binding Protein 1;  Insulin-Like Growth Factor Binding Protein 3;  Insulin-Like Growth Factor I;  Linkage Disequilibrium;  Male;  Middle Aged;  Polymorphism, Single Nucleotide;  Prostatic Neoplasms;  Risk Factors",
    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) ≥ 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 (Padj = 8.8 × 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 × 10-3. IGF-I levels were significantly associated with PCa risk (Ptrend = 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. © The Author 2010. Published by Oxford University Press. All rights reserved."
}