Association of IL-6 Promoter and Receptor Polymorphisms with Multiple Myeloma Risk: A Systematic Review and Meta-Analysis

Background: A number of studies show that the pleiotropic cytokine interleukin-6 (IL-6) plays an important role in the pathogenesis of multiple myeloma (MM). However, whether MM risk is associated with IL-6 genetic variability remains uncertain.

Objective: The aim of our study was to evaluate the association between two different IL-6 polymorphisms (located in the IL-6 promoter and receptor, respectively) and the risk of developing MM using a meta-analytic approach.

Materials And Methods: A systematic search for studies on the association of IL-6/IL-6R single-nucleotide polymorphisms with susceptibility to MM was conducted in PubMed, Cochrane Library, Embase, CNKI (Chinese) and Wanfang (Chinese) Digital Dissertations Databases from inception through November 2014. A meta-analysis was performed and results were presented as odds ratios (ORs) with 95% confidence intervals (CIs).

Results: A total of eight case-control studies on the IL-6 promoter polymorphism and three studies on the IL-6 receptor (IL-6R) polymorphism were included. No significant association was found between the IL-6 promoter rs1800795 (G>C) polymorphism and MM susceptibility. A significantly increased risk of MM was observed with the IL-6R rs8192284 (A>C) polymorphism. In subgroup analyses, grouped by ethnicity, region, quality of studies, and Hardy-Weinberg equilibrium of control group, similar results were found.

Conclusion: Unlike the IL-6 promoter rs1800795 (G>C) polymorphism, the IL-6R rs8192284 (A>C) polymorphism may be associated with MM risk. However, large-scale studies are needed to validate our findings since they are based on a relatively small number of studies.