PURPOSE: Interleukin-6(IL-6) has an important role duringprostate cancerprogression and IL-6 levels in the serum of patients with hormone refractory and metastaticprostate cancerare significantly increased compared with those in patients with hormone sensitive and localizedprostate cancer. The G>Cpolymorphismat position -174 in the promoter of the IL-6 gene has beenassociatedwith differences in IL-6 transcription in vitro and IL-6 protein levels in vivo. We determined the association of IL-6polymorphismwithprostate cancerprogression. MATERIALS AND METHODS: : We examined the association of IL-6polymorphismwith the risk of advanced disease in 95 patients with different stages ofprostate cancerusing the tetra-primer polymerase chain reaction genotyping method. RESULTS: : We found that the -174G>C genotype of IL-6 gene wasassociatedwith an overall increased risk of advancedprostate 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 significantlyassociatedwith increased serumprostatespecific antigen (p = 0.004) and with recurrentprostate cancercompared with GG homozygotes (p = 0.027). CONCLUSIONS: : These data demonstrate a strong association of the -174G>Cpolymorphismof the IL-6 gene with the aggressiveness and recurrence ofprostate cancer, suggesting thatgeneticpredisposition ofgeneticdifferences in the human IL-6 gene could be linked to the risk of recurrentprostate cancer.