Interleukin-6 polymorphism is associated with more aggressive prostate cancer

Purpose: Interleukin-6 (IL-6) has an important role during prostate cancer progression and IL-6 levels in the serum of patients with hormone refractory and metastatic prostate cancer are significantly increased compared with those in patients with hormone sensitive and localized prostate cancer. The G > C polymorphism at position -174 in the promoter of the IL-6 gene has been associated with differences in IL-6 transcription in vitro and IL-6 protein levels in vivo. We determined the association of IL-6 polymorphism with prostate cancer progression. Materials and Methods: We examined the association of IL-6 polymorphism with the risk of advanced disease in 95 patients with different stages of prostate cancer using the tetra-primer polymerase chain reaction genotyping method. Results: We found that the -174G > C genotype of IL-6 gene was associated with an overall increased risk of advanced prostate cancer. A strong association between this genotype and Gleason score was observed at the - 174G > C locus of the IL-6 gene (p < 0.001). The distribution of this genotype was also significantly different between stages T3-T4 and T1-T2 tumors (p < 0.001). In addition, the IL-6 genotype was linked with vascular invasion (p = 0.024), seminal vesicle involvement (p = 0.006) and capsular invasion (p < 0.001). Furthermore, the -174G > C genotype of the IL-6 gene was significantly associated with increased serum prostate specific antigen (p = 0.004) and with recurrent prostate cancer compared with GG homozygotes (p = 0.027). Conclusions: These data demonstrate a strong association of the - 174G > C polymorphism of the IL-6 gene with the aggressiveness and recurrence of prostate cancer, suggesting that genetic predisposition of genetic differences in the human IL-6 gene could be linked to the risk of recurrent prostate cancer.