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
| Autor: | Patricia L. Blount, Peter S. Rabinovitch, Johanna N. Lampe, SKay Lewis, Thomas L. Vaughan, Brian J. Reid, Robert J. Freeman, Kamran Ayub, Chu Chen, Robert D. Odze, Sid H. Siahpush |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Esophageal Neoplasms Genotype Epidemiology medicine.medical_treatment Aneuploidy Adenocarcinoma Gastroenterology Receptor IGF Type 1 Barrett Esophagus Insulin-like growth factor Internal medicine medicine Humans Longitudinal Studies Insulin-Like Growth Factor I Esophagus Ploidies Polymorphism Genetic business.industry Esophageal disease Hazard ratio Middle Aged medicine.disease Insulin-Like Growth Factor Binding Proteins Insulin-Like Growth Factor Binding Protein 3 medicine.anatomical_structure Endocrinology Oncology Tumor progression Barrett's esophagus Disease Progression Female business |
| Zdroj: | Cancer Epidemiology, Biomarkers & Prevention. 16:2387-2395 |
| ISSN: | 1538-7755 1055-9965 |
| DOI: | 10.1158/1055-9965.epi-06-0986 |
| Popis: | 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. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2387–96) |
| Databáze: | OpenAIRE |
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