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

Genet Test Mol Biomarkers. 2016 Oct;20(10):587-596. doi: 10.1089/gtmb.2015.0169. Epub 2016 Aug 15.

Abstract

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.

Keywords: IL-6 promoter; IL-6 receptor; SNPs; meta-analysis; multiple myeloma.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Genetic Predisposition to Disease*
  • Humans
  • Interleukin-6 / genetics*
  • Multiple Myeloma / genetics*
  • Neoplasm Proteins / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Receptors, Interleukin-6 / genetics

Substances

  • IL6 protein, human
  • IL6R protein, human
  • Interleukin-6
  • Neoplasm Proteins
  • Receptors, Interleukin-6