Longitudinal study of insulin-like growth factor, insulin-like growth factor binding protein-3, and their polymorphisms: Risk of neoplastic progression in Barrett's esophagus

Abstract

Background: Insulin-like growth factor-I (IGF-I) is a potent mitogen. IGF-I and its main binding protein, IGF binding protein-3 (IGFBP-3), and their polymorphisms have been investigated in relation to risk of many cancers, but not esophageal adenocarcinoma. Materials and Methods: We used data and specimens from a longitudinal study of persons with Barrett's esophagus (n = 344; median, 5.4 years follow up) to determine whether baseline serum concentrations of IGF-I and IGFBP-3 and associated polymorphisms were related to the risk of developing esophageal adenocarcinoma or flow cytometric abnormalities. Results: Overall, circulating concentrations of IGF-I and IGBP-3 were not associated with risk of esophageal adenocarcinoma or flow cytometric abnormalities, with the exception of an approximate tripling of risk of aneuploidy among participants with higher IGFBP-3 levels [above median; adjusted hazard ratio (HR) comparing subjects with levels lower than median versus higher of equal to median, 2.7; 95% confidence interval (95% CI), 1.2-6.0; P = 0.01]. Genotypic analyses revealed that persons with the IGF-I [cytosine-adenine (CA)]19 or the IGFBP-3 A-202C C allele were associated with lower circulating concentrations of IGF-I (Ptrend = 0.01) and IGFBP-3 (Ptrend = 0.002), respectively. Persons with two copies of the IGF-I receptors 2-bp deletion allele had a nonsignificant 2-fold increased risk of tetraploidy (HR, 2.3; 95% CI, 0.9-5.9; Ptrend = 0.11). After adjustment for IGFBP-3 levels, participants carrying two IGFBP-3 C alleles had a significantly higher risk of developing aneuploidy (HR, 3.8; 95% CI, 1.0-14.0; Ptrend = 0.04) than carriers of A alleles; whereas no associations were observed between the outcomes studied and the IGF-I receptors AGG trinucleotide repeat polymorphism at position 97. Conclusion: Our findings, although based on a relatively small number of outcomes and subject to several limitations, indicate a potential role of the complex IGF system in neoplastic progression among persons with Barrett's esophagus. Copyright © 2007 American Association for Cancer Research.