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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.

Authors: Siahpush, Sid H  Vaughan, Thomas L  Lampe, Johanna N  Freeman, Robert  Lewis, Skay  Odze, Robert D  Blount, Patricia L  Ayub, Kamran  Rabinovitch, Peter S  Reid, Brian J  Chen, Chu 
Citation: Siahpush SH, etal., Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2387-95.
Pubmed: (View Article at PubMed) PMID:18006928
DOI: Full-text: DOI:10.1158/1055-9965.EPI-06-0986


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 (P(trend)=0.01) and IGFBP-3 (P(trend)=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; P(trend)=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; P(trend)=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.

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CRRD Object Information
CRRD ID: 12743582
Created: 2017-02-08
Species: All species
Last Modified: 2017-02-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.