Implications for prostate cancer of insulin-like growth factor-I (IGF-I) genetic variation and circulating IGF-I levels

J Clin Endocrinol Metab. 2007 Dec;92(12):4820-6. doi: 10.1210/jc.2007-0887. Epub 2007 Oct 2.

Abstract

Background: Elevated levels of circulating IGF-I have consistently been associated with increased prostate cancer risk. We recently found a haplotype in the 3' region of the IGF-I gene associated with increased risk of prostate cancer, and we hypothesized that the observed association is mediated by circulating IGF-I.

Materials and methods: We analyzed haplotypes and three haplotype-tagging single nucleotide polymorphisms (htSNPs) in the 3' region of the IGF-I gene in relation to circulating levels IGF-I in 698 control subjects from the CAncer Prostate in Sweden (CAPS) study and 575 cases and controls from the prospective Northern Sweden Health and Disease Cohort (NSHDC) study. We also performed a meta-analysis of these two and four other association studies on genetic variation in the 3' region of the IGF-I gene in relation to circulating IGF-I levels.

Results: The IGF-I haplotype previously associated with prostate cancer risk, labeled "TCC," was associated with elevated levels of IGF-I in the CAPS study (P = 0.02), but not in the NSHDC study. In contrast, two of the three IGF-I htSNPs tagging this haplotype, rs6220 and rs7136446, were associated with elevated levels of IGF-I in the NSHDC (P = 0.03 and P = 0.04, respectively), but not in the CAPS study. In the meta-analysis, the TCC haplotype and the rs6220 SNP were associated with elevated levels of circulating IGF-I (P = 0.001 and P < 0.0001, respectively).

Conclusions: Genetic variation in the 3' region of the IGF-I gene seems to influence circulating levels of IGF-I. This observation is consistent with the hypothesis that variation in the IGF-I gene plays a role in prostate cancer susceptibility by influencing circulating levels of IGF-I.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cohort Studies
  • Gene Dosage
  • Gene Frequency
  • Genetic Variation
  • Genotype
  • Haplotypes
  • Heterozygote
  • Humans
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / metabolism*
  • Logistic Models
  • Male
  • Polymorphism, Single Nucleotide
  • Prostatic Neoplasms / genetics*
  • Sweden / epidemiology

Substances

  • Insulin-Like Growth Factor I