Polymorphism in the microglial cell-mobilizing CX3CR1 gene is associated with survival in patients with Glioblastoma

Rodero, Mathieu, Yannick, Marie, Couder, Mathieu, Blondet, Emmeline, Mokhtari, Karima, Rousseau, Audrey, Raoul, William, Carpentier, Catherine, Sennlaub, Florian, Deterre, Philippe, Delattre, Jean-Yves, Debré, Patrice, Sanson, Marc and Combadière, Christophe (2008) Polymorphism in the microglial cell-mobilizing CX3CR1 gene is associated with survival in patients with Glioblastoma. Journal of Clinical Oncology, 26 36: 5957-5964. doi:10.1200/JCO.2008.17.2833

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Author Rodero, Mathieu
Yannick, Marie
Couder, Mathieu
Blondet, Emmeline
Mokhtari, Karima
Rousseau, Audrey
Raoul, William
Carpentier, Catherine
Sennlaub, Florian
Deterre, Philippe
Delattre, Jean-Yves
Debré, Patrice
Sanson, Marc
Combadière, Christophe
Title Polymorphism in the microglial cell-mobilizing CX3CR1 gene is associated with survival in patients with Glioblastoma
Journal name Journal of Clinical Oncology   Check publisher's open access policy
ISSN 0732-183X
Publication date 2008-12-20
Sub-type Article (original research)
DOI 10.1200/JCO.2008.17.2833
Open Access Status File (Publisher version)
Volume 26
Issue 36
Start page 5957
End page 5964
Total pages 8
Place of publication Alexandria, Virginia, U.S.
Publisher American Society of Clinical Oncology
Language eng
Subject 1112 Oncology and Carcinogenesis
Formatted abstract
Few reliable prognostic molecular markers have been characterized for glioblastoma multiforme (GBM), considered the deadliest of human cancers. We hypothesized that genetic polymorphisms in chemokines and their receptors, which together control microglial cell mobilization, may influence survival.
Methods: Distributions of one polymorphism of the chemokine CCL2 (–2518A<G) and two polymorphisms of the chemokine receptor CX3CR1 (termed V249I and T280M) were determined in a prospective series of 230 patients with GBM and correlated with overall survival. The replication study used data from a retrospective series of 106 additional patients with GBM. The extent of microglial cell infiltration was assessed by immunochemistry in 102 tumor specimens.
Results: Survival analysis showed that the common CX3CR1-I249 allele was an independent favorable prognostic factor in both groups, prospective and retrospective, with hazard ratios of 0.619 (95% CI, 0.451 to 0.850; P = .0031) and 0.354 (95% CI, 0.217 to 0.580; P < .0001), respectively. This beneficial effect was observed only in patients who underwent surgery. Patients with only this CX3CR1-I249 allele had a substantially longer mean survival (23.5 v 14.1 months; P < .0001). The CCL2-2518G allele was not associated with patient survival. Immunohistochemical analysis of primary tumor biopsies showed that the common CX3CR1 variant allele was associated with reduced microglial cell infiltration.
Conclusion :The common CX3CR1 allelic variant was associated with increased GBM survival and with reduced tumor infiltration by microglia. The CX3CR1 polymorphism does not seem to be a risk factor for GBM but may prove useful in predicting survival. 
Keyword Glioblastoma multiforme
Microglial cell mobilization
Microglial cell infiltration
Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Centre for Clinical Research Publications
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