title: Influence of fractalkine receptor gene polymorphisms V249I-T280M on cancer occurrence after renal transplantation.
abstract: BACKGROUND
  Fractalkine (CX3CL1) and its receptor (CX3CR1) are involved in antitumor immunity. Two common single nucleotide polymorphisms of the CX3CR1 gene, V249I and T280M, have been associated with reduced fractalkine signaling characterized by decreased adhesive function, signaling, and chemotaxis of leukocytes. We hypothesized that a renal transplant recipient (RTR) carrying the homozygous I249M280 genotype could experience more cancer due to lower CX3CL1-dependent antitumorigenic effects.
  
  
  METHODS
  We studied the association between these polymorphisms and cancer incidence in two independent cohorts of RTR, including a total of 622 patients.
  
  
  RESULTS
  The median follow-up was 8.7 and 7.9 years for the first and second cohorts, respectively. Analysis of 622 patients identified 20 (3.2%) I249M280 homozygous patients, 321 (51.6%) V249T280 homozygous patients, and 281 (45.2%) heterozygous patients. I249M280 homozygotes have an independent increased risk of cancer (hazard ratio [95% confidence interval], 3.3 [1.04-10.52], P=0.043 for cohort 1 and 9.2 [1.67-50.91], P=0.011 for cohort 2) compared with other patients. Age and male gender were also risk factors for cancer occurrence.
  
  
  CONCLUSIONS
  CX3CR1 gene polymorphism is associated with a higher rate of cancer in RTRs. Such findings may be used to influence immunosuppressive strategies and optimize patient management.
authors: INSERM, UMR645, Université de Franche-Comté, Etablissement Français du Sang, IFR133, Besançon, France. ccourivaud@chu-besancon.fr
authors: Cécile
authors: C
authors: Courivaud
authors: Jamal
authors: J
authors: Bamoulid
authors: Alexandre
authors: A
authors: Loupy
authors: Marina
authors: M
authors: Deschamps
authors: Christophe
authors: C
authors: Ferrand
authors: Dominique
authors: D
authors: Simula-Faivre
authors: Pierre
authors: P
authors: Tiberghien
authors: Jean-Marc
authors: JM
authors: Chalopin
authors: Christophe
authors: C
authors: Legendre
authors: Eric
authors: E
authors: Thervet
authors: Christophe
authors: C
authors: Borg
authors: Philippe
authors: P
authors: Saas
authors: Didier
authors: D
authors: Ducloux
mesh_terms: D000328:Adult; D000073883:CX3C Chemokine Receptor 1; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D019707:Receptors, Chemokine / Q000235:genetics*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D019707:Receptors, Chemokine