TY - JOUR
TI - 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
AU - Schumacher, F.R.
AU - Cheng, I.
AU - Freedman, M.L.
AU - Mucci, L.
AU - Allen, N.E.
AU - Pollak, M.N.
AU - Hayes, R.B.
AU - Stram, D.O.
AU - Canzian, F.
AU - Henderson, B.E.
AU - Hunter, D.J.
AU - Virtamo, J.
AU - Manjer, J.
AU - Gaziano, J.M.
AU - Kolone, L.N.
AU - Tjønneland, A.
AU - Albanes, D.
AU - Calle, E.E.
AU - Giovannucci, E.
AU - David Crawford, E.
AU - Haiman, C.A.
AU - Kraft, P.
AU - Willett, W.C.
AU - Thun, M.J.
AU - Le Marchand, L.
AU - Kaaks, R.
AU - Feigelson, H.S.
AU - Bueno-de-Mesquita, H.B.
AU - Palli, D.
AU - Riboli, E.
AU - Lund, E.
AU - Amiano, P.
AU - Andriole, G.
AU - Dunning, A.M.
AU - Trichopoulos, D.
AU - Stampfer, M.J.
AU - Key, T.J.
AU - Ma, J.
JO - Human Molecular Genetics
PY - 2010
VL - 19
TODO - 15
SP - 3089-3101
PB - 
SN - 0964-6906, 1460-2083
TODO - 10.1093/hmg/ddq210
TODO - 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
TODO - 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.
ER -