Association of Polymorphisms in Cytokine genes with susceptibility to Precancerous Lesions and Cervical Cancer: A systematic review with meta-analysis

Objectives This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical cancer and HPV infection through a systematic review with meta-analysis. To verify the effect of SNPs, we also analyzed the transcription factor binding affinity using bioinformatics tools. Methods Seven electronic databases (MEDLINE, Scielo, BIREME, PubMed, Scopus, Web of Science and Science Direct) were searched for case-control studies. Results A total of 35 relevant case-control studies were meta-analyzed, including 7 cytokine genes and 15 SNPs. SNPs inIL-17A(rs2275913, rs3748067);IL-17 F(rs763780);IL-12A(rs568408);IL-12B(rs3212227);TNFA(rs1800629, rs361525);IL-1B(rs16944);IL-6(rs1800795);IL-10(rs1800896) genes were associated with increased risk for cervical cancer. No association was observed between meta-analyzed polymorphisms and SIL. Additional bioinformatics analysis suggested a possible transcriptional regulation pathway of theTNFAandIL-10genes through the MZF1 (TNFA-308 G > A andIL-10 - 1082A>G) and ZNF263 (TNFA-238 G > A) transcription factors binding. Conclusion Overall, 10 SNPs in cytokine genes were associated with increased risk for cervical cancer. Therefore, in our meta-analysis, these SNPs demonstrated to be potential biomarkers for predicting or identifying cases of high risk for SIL and cervical cancer.