TY - JOUR
T1 - 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
AU - Schumacher, Fredrick R.
AU - Cheng, Iona
AU - Freedman, Matthew L.
AU - Mucci, Lorelei
AU - Allen, Naomi E.
AU - Pollak, Michael N.
AU - Hayes, Richard B.
AU - Stram, Daniel O.
AU - Canzian, Frederico
AU - Henderson, Brian E.
AU - Hunter, David J.
AU - Virtamo, Jarmo
AU - Manjer, Jonas
AU - Gaziano, J. Michael
AU - Kolonel, Laurence N.
AU - Tjonneland, Anne
AU - Albanes, Demetrius
AU - Calle, Eugenia E.
AU - Giovannucci, Edward
AU - Crawford, E. David
AU - Haiman, Christopher A.
AU - Kraft, Peter
AU - Willett, Walter C.
AU - Thun, Michael J.
AU - Marchand, Loic Le
AU - Kaaks, Rudolf
AU - Feigelson, Heather Spencer
AU - Bueno-de-Mesquita, H. Bas
AU - Palli, Domenico
AU - Riboli, Elio
AU - Lund, Eliv
AU - Amiano, Pilar
AU - Andriole, Gerald
AU - Dunning, Alison M.
AU - Trichopoulos, Dimitrios
AU - Stampfer, Meir J.
AU - Key, Timothy J.
AU - Ma, Jing
PY - 2010
Y1 - 2010
N2 - 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 (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.
AB - 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 (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.
U2 - 10.1093/hmg/ddq210
DO - 10.1093/hmg/ddq210
M3 - Article
C2 - 20484221
SN - 0964-6906
VL - 19
SP - 3089
EP - 3101
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 15
ER -
