Influence of fractalkine receptor gene polymorphisms V249I-T280M on cancer occurrence after renal transplantation.

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.