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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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 (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.

Detaljer

Författare
  • Fredrick R. Schumacher
  • Iona Cheng
  • Matthew L. Freedman
  • Lorelei Mucci
  • Naomi E. Allen
  • Michael N. Pollak
  • Richard B. Hayes
  • Daniel O. Stram
  • Frederico Canzian
  • Brian E. Henderson
  • David J. Hunter
  • Jarmo Virtamo
  • J. Michael Gaziano
  • Laurence N. Kolonel
  • Anne Tjonneland
  • Demetrius Albanes
  • Eugenia E. Calle
  • Edward Giovannucci
  • E. David Crawford
  • Christopher A. Haiman
  • Peter Kraft
  • Walter C. Willett
  • Michael J. Thun
  • Loic Le Marchand
  • Rudolf Kaaks
  • Heather Spencer Feigelson
  • H. Bas Bueno-de-Mesquita
  • Domenico Palli
  • Elio Riboli
  • Eliv Lund
  • Pilar Amiano
  • Gerald Andriole
  • Alison M. Dunning
  • Dimitrios Trichopoulos
  • Meir J. Stampfer
  • Timothy J. Key
  • Jing Ma
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik
Originalspråkengelska
Sidor (från-till)3089-3101
TidskriftHuman Molecular Genetics
Volym19
Utgivningsnummer15
StatusPublished - 2010
PublikationskategoriForskning
Peer review utfördJa