Serum concentration of interleukin‐35 and its association with tumor stages and FOXP3 gene polymorphism in patients with prostate cancer
&NA; IL‐35 is an immunosuppressive cytokine that is largely synthesized by regulatory T (Treg) cells and may inhibit antitumor immune responses. This investigation aimed to determine the serum IL‐35 concentrations and a single nucleotide polymorphism (SNP) in position of rs3761548, within the promoter region of FOXP3 gene, in patients with prostate cancer (PC). The blood specimens were obtained from 150 PC patients prior to using radiation therapy, chemo‐ or immunotherapy and 150 age‐matched healthy men as a control group. The serum IL‐35 concentrations and the pattern of genetic variation at position of rs3761548 were assessed using ELISA and polymerase chain reaction‐restriction fragment length polymorphism (PCR–RFLP), respectively. The mean serum IL‐35 concentrations were significantly higher in PC patients when compared with healthy control group (20.01 ± 7.03 Pg/mL vs. 11.60 ± 2.49 Pg/mL, P < 0.001). The serum IL‐35 concentrations raised with progression of PC stages so that there was a significant difference between PC stages concerning the IL‐35 concentrations (P < 0.001). The mean serum IL‐35 concentrations in patients with Gleason scores of 1–6 and Gleason scores 7–10 were significantly higher as compared with healthy controls (P < 0.001). Moreover, the serum IL‐35 concentrations in patients with having Gleason scores of 7–10 were significantly higher as compared with patients with Gleason scores of 1–6 (P < 0.001). Evaluation of the genetic variations in position SNP rs3761548 revealed that the AA genotype and A allele were more prevalent whereas CC genotype and C allele were less prevalent in PC patients when compared with healthy men (P < 0.01, P < 0.001, P < 0.002 and P < 0.001, respectively). The AA genotype and A allele were associated with higher risk of PC incidence [OR: 2.42 (95% CI: 1.179–4.99); P < 0.001 and OR: 1.732 (95% CI: 1.244 – 2.413); P < 0.001, respectively]. The mean serum IL‐35 concentrations were significantly higher in total subjects (PC patients + healthy individuals) with AA genotype and A allele than individuals with CC genotype and C allele at SNP rs3761548 (P < 0.05 and P < 0.01, respectively). Higher serum IL‐35 concentrations observed in patients with PC that were increased with progressive tumor stages. These findings indicate that the IL‐35 is possibly involve in tumor progression. Moreover, SNP rs3761548 may affect the susceptibility to PC and the serum IL‐35 concentrations.