Analysis of Interleukin-6 Gene Variants ( rs1800795 , rs1800796 , rs1554606 , rs1800797 , rs2069840 , rs12700386 , and rs2069861 ) as Prognostic Markers in Breast Cancer: A Systematic Review, Meta-Analysis, and Network Analysis.

Interleukin-6 (IL-6) has obviously tumor-promoting and tumor-inhibitory effects and can induce an epithelial-mesenchymal transition phenotype in human breast cancer (BC) cells and implicate its potential to promote BC metastasis. Herein, we aimed to evaluate the association of IL-6 variants ( rs1800795 , rs1800796 , rs1554606 , rs1800797 , rs2069840 , rs12700386 , and rs2069861 ) with the susceptibility to BC. The databases of PubMed/Medline, Web of Science, Scopus, and Cochrane Library were searched until December 19, 2022, without any restrictions. The quality assessment of each study was performed based on the Newcastle-Ottawa Scale tool. The Review Manager 5.3 software presented the effect sizes including odds ratio (OR) along with a 95% confidence interval (CI). Both publication bias and sensitivity analyses were carried out by the Comprehensive Meta-Analysis version 2.0 software. A total of 2,508 records were identified among databases and at last, 27 articles were entered into the meta-analysis. Seven polymorphisms of IL-6 were entered into the analyses. Just rs1800797 polymorphism in the dominant model (OR = 1.51; 95% CI = 1.15-2.00; P  = 0.003) and rs2069840 polymorphism in heterozygous (OR = 0.89; 95% CI = 0.81-0.97; P  = 0.008) and dominant (OR = 0.91; 95% CI = 0.84-0.99; P  = 0.02) models had a significant association with the BC risk. In conclusion, among 7 polymorphisms and despite a few included cases, the present meta-analysis recommended that the AA+GA genotype of rs1800797 polymorphism had a significantly elevated risk and the GC and the CC+GC genotypes of rs2069840 polymorphism had a protective role in the BC patients.