Polymorphism in the microglial cell-mobilizing CX3CR1 gene is associated with survival in patients with glioblastoma.
OBJECTIVE
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.


CONCLUSIONS
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.
Rodero
Mathieu
M
Laboratoire d'Immunologie Cellulaire, L'Institut National de Santé et de Recherche Médicale U543, Paris, France.
Marie
Yannick
Y
Coudert
Mathieu
M
Blondet
Emmeline
E
Mokhtari
Karima
K
Rousseau
Audrey
A
Raoul
William
W
Carpentier
Catherine
C
Sennlaub
Florian
F
Deterre
Philippe
P
Delattre
Jean-Yves
JY
Debré
Patrice
P
Sanson
Marc
M
Combadière
Christophe
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000166:cytology*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D019707:Receptors, Chemokine / Q000235:genetics*; D012189:Retrospective Studies
D019707:Receptors, Chemokine