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

ABSTRACT

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 in IL-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 the TNFA and IL-10 genes through the MZF1 (TNFA −308 G > A and IL-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.

KEYWORDS:

• SNP
• cytokine genes
• human Papillomavirus
• cervical cancer

Acknowledgments

This study had financial support from Coordination for the Improvement of Higher Education Personnel (CAPES) and Research Support Foundation of Alagoas State (FAPEAL). The authors acknowledge to Cancer Prevention and Diagnosis Center (NPDC) from Arapiraca-AL, Brazil.

Declaration of interest statement

All authors declare that there are no conflicts of interest.

Additional information

Funding

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [23038.023347/2016-74]; Fundação de Amparo à Pesquisa do Estado de Alagoas [23038.023347/2016-74].