Genetic variation in insulin-like growth factors and brain tumor risk
| Autor: | Robert G. Selker, Howard A. Fine, Peter D. Inskip, Amy Hutchinson, Nathaniel Rothman, Stefan Lönn, Jay S. Loeffler, Peter McL. Black, William R. Shapiro |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Adolescent medicine.medical_treatment IGFBP3 Biology Polymorphism Single Nucleotide Somatomedins Glioma Internal medicine medicine Humans Genetic Predisposition to Disease Receptor Aged Insulin-like growth factor 1 receptor Aged 80 and over Brain Neoplasms Cell growth Growth factor Cancer Middle Aged medicine.disease nervous system diseases Endocrinology Oncology Case-Control Studies Basic and Translational Investigations Cancer research Female Neurology (clinical) Adult stem cell |
| Zdroj: | Neuro-Oncology. 10:553-559 |
| ISSN: | 1523-5866 1522-8517 |
| DOI: | 10.1215/15228517-2008-026 |
| Popis: | The insulin-like growth factor (IGF) system comprises two ligands (IGF-1 and IGF-2), the IGF-1 and IGF-2 receptors, six binding proteins (IGFBP-1 to -6), and various IGFBP-related peptides.1 IGF-1 is the major physiological mediator of the effect of growth hormone and therefore has a strong influence on cell proliferation and differentiation. It also inhibits apoptosis by blocking initiation of the apoptotic pathway.1 The IGF-1 receptor (IGF-1R) mediates the action of IGF-1 and is involved in oncogenic transformation processes.1 IGFBPs modulate the interaction between IGF-1 and IGF-1R but also have independent effects on cell growth.1–3 IGFBP-3 has an inhibitory effect on IGF-1 activity and also acts as an apoptotic agent.1 IGFBP-3 also has been recognized to exhibit a number of growth-promoting effects. Experimental studies have shown that alterations in IGF function can influence cellular transformation and tumor cell proliferation. IGF1, IGF2, and IGF1R genes have all been reported to be overexpressed in glioma and meningioma as well as in a wide range of other human cancers, including breast, leukemia, lung, thyroid, and prostate.4 IGFs, together with their receptors and binding proteins, have been reported to be associated with cancer risk.5,6 Epidemiological studies have suggested that genetic variation in IGF1, IGF1R, and IGFBP3 may be related to breast, prostate, and colorectal cancer risk.7–10 In vitro studies have demonstrated that IGF receptors and binding proteins promote mitogenesis and differentiation in glial cells, oligodendrocytes, neuronal cells, adult stem cells, and brain explants and regulate axon myelination.4 Furthermore, observations in the literature suggest that IGF gene pathways show similar expression and functional features during fetal development and tumorigenesis.11 There is, however, little epidemiologic data concerning the possible involvement of IGF signaling in the development of brain tumors in humans. A recent small prospective study indicated an inverse association between glioma and IGF-1 serum levels.12 We hypothesized that polymorphisms in IGF genes are risk factors for glioma and meningioma. To test the hypothesis, we examined associations with several IGF gene variants in the context of a case-control study. |
| Databáze: | OpenAIRE |
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