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

• Published in: Immunological investigations 2021-07, Vol.50 (5), p.492-526
• Main Authors: de Moura, Edilson Leite, dos Santos, Ana Caroline Melo, da Silva, Denise Macedo, dos Santos, Bruna Brandão, Figueredo, Diego de Siqueira, Moura, Alexandre Wendell Araújo, da Silva, Adriely Ferreira, Tanabe, Ithallo Sathio Bessoni, de Lira Tanabe, Eloiza Lopes, Lira Neto, Abel Barbosa, Pereira e Silva, Aline Cristine, de Carvalho Fraga, Carlos Alberto, de Lima Filho, José Luiz, de Farias, Karol Fireman, Martins de Souza, Elaine Virginia
• Format: Article
• Language: English
• Subjects: Alphapapillomavirus - physiology; cervical cancer; Computational Biology; cytokine genes; Cytokines - genetics; Female; Genetic Predisposition to Disease; human Papillomavirus; Humans; Papillomavirus Infections - genetics; Papillomavirus Infections - immunology; Polymorphism, Single Nucleotide; Precancerous Conditions - genetics; Risk; SNP; Squamous Intraepithelial Lesions of the Cervix - genetics; Squamous Intraepithelial Lesions of the Cervix - immunology; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - immunology
• ISSN: 0882-0139; 1532-4311
• DOI: 10.1080/08820139.2020.1778023

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.