Kaiping Zhang, Li Zhang, Jun Zhou, Zongyao Hao, Song Fan, Cheng Yang, Chaozhao Liang

Interleukin-6 (IL-6) is a multifunctional proinflammatory cytokine involved in cancer initiation and progression. Numerous studies have investigated the associations between IL-6 polymorphisms (IL-6 -174G>C, -592G>C, -597G>A) and risk of urinary system cancers, including prostate cancer, bladder cancer, and renal cell cancer. However, conclusions from these studies were controversial. Thus, we conducted the current meta-analysis to obtain the comprehensive profile regarding the association between IL-6 polymorphisms and urinary system cancer risk. According to inclusion and exclusion criteria, the associations of IL-6 polymorphisms with urinary system cancer were searched from database and analyzed using STATA 12.0 statistical software. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 20 previous publications consisting of 15,033 cases and 17,655 controls were involved in this meta-analysis. Significant association was observed in overall population regarding IL-6 -592G>C polymorphisms (G vs C: OR =0.1.30, 95% CI =1.13-2.52; GG vs CC: OR =1.81, 95% CI =1.31-2.52; GG vs GC + CC: OR =1.33, 95% CI =1.02-1.75; GG + GC vs CC: OR =1.41, 95% CI =1.09-1.83). In the stratified analyses by ethnicity, the significant associations were found among Asian (GG vs CC: OR =1.89, 95% CI =1.34-2.66; GG + GC vs CC: OR =1.43, 95% CI =1.09-1.87) and Black population (GC vs CC: OR =0.20, 95% CI =0.05-0.82) rather than Caucasian men. Likewise, there were noticeable associations in almost all the other subanalyses such as cancer types, control sources, genotyped methods, and sample sizes. However, no significant associations were identified between any of IL-6 -174G>C polymorphisms with urinary system cancer, except for Asian population (G vs C: OR =0.81, 95% CI =0.70-0.95; GG vs CC: OR =0.51, 95% CI =0.35-0.74; GC vs CC: OR =0.49, 95% CI =0.33-0.72; GG + GC vs CC: OR =0.50, 95% CI =0.35-0.72; respectively). In addition, no significant associations were detected between IL-6 -597G>A polymorphism and urinary system cancer, regardless of whole or subgroups. This meta-analysis presents a relatively comprehensive view of the associations between IL-6 polymorphism and urinary system cancer risk to explore the carcinogenic mechanisms, which will help shed light on the clinical diagnosis and therapy for urinary system cancer. However, further detailed studies are needed to verify our conclusion.