Association between interleukin-6 polymorphisms and urinary system cancer risk: evidence from a meta-analysis

Abstract

BackgroundInterleukin-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.MethodsAccording 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.ResultsA 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.ConclusionThis 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.

Association of interleukin 6 -174 G/C polymorphism with coronary artery disease and circulating IL-6 levels: a systematic review and meta-analysis

“…Interleukin 6 (IL-6) is a circulating bioactive peptide of 23.7 kDa and acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. This endogenous pyrogen primarily originates from mononuclear phagocytes but also, in part, from fibroblasts, T and B lymphocytes and vascular endothelial cells [ 1 , 2 ]. It functions in inflammation and maturation of B cells [ 3 ], and is encoded by IL6 gene (located at chromosome 7p21–14) which is known to have several polymorphic variants [ 4 ].…”

Single nucleotide polymorphism of transforming growth factor-β1 and interleukin-6 as risk factors for ovarian cancer

“…The IL-6 polymorphism has been regarded as a crucial modulator in pathogenesis of various types of cancer [30][31][32][33][34]. However, allelic distributions of various polymorphisms in IL-6 gene could vary geographically and ethnically, thus leading to discordant findings between these polymorphisms and cancer risk.…”

Prostate-specific IL-6 transgene autonomously induce prostate neoplasm through amplifying inflammation in the prostate and peri-prostatic adipose tissue

“…Polymorphisms of IL-6 gene have been associated with prostate cancer risk [26–28]; however, bona fida evidence of IL-6 as a sole factor in prostate cancer risk is lacking. Most of pro-tumorigenic evidence of IL-6 in prostate cancer was achieved from experiments of oncogene-immortalized cell lines or clinical correlation studies.…”