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

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Association of Polymorphisms in Cytokine genes with susceptibility to Precancerous Lesions and Cervical Cancer: A systematic review with meta-analysis
Immunological Investigations ( IF 2.9 ) Pub Date : 2020-06-30 , DOI: 10.1080/08820139.2020.1778023
Edilson Leite de Moura _{1,

2} , Ana Caroline Melo Dos Santos _{1,

2} , Denise Macedo da Silva _{1,

2} , Bruna Brandão Dos Santos _{1,

2} , Diego de Siqueira Figueredo , Alexandre Wendell Araújo Moura ₁ , Adriely Ferreira da Silva ₁ , Ithallo Sathio Bessoni Tanabe _{1,

2} , Eloiza Lopes de Lira Tanabe _{1,

2} , Abel Barbosa Lira Neto _{1,

2} , Aline Cristine Pereira E Silva ₁ , Carlos Alberto de Carvalho Fraga _{1,

3} , José Luiz de Lima Filho ₄ , Karol Fireman de Farias ₁ , Elaine Virginia Martins de Souza _{1,

2}

Affiliation

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.

中文翻译：

细胞因子基因多态性与癌前病变和宫颈癌易感性的关联：荟萃分析的系统评价

摘要

目的：本研究通过荟萃分析的系统评价，研究细胞因子基因中的单核苷酸多态性 (SNP) 与鳞状上皮内病变 (SIL)、宫颈癌和 HPV 感染的易感性之间的关系。为了验证 SNP 的影响，我们还使用生物信息学工具分析了转录因子结合亲和力。

方法：检索了七个电子数据库（MEDLINE、Scielo、BIREME、PubMed、Scopus、Web of Science 和 Science Direct）以进行病例对照研究。

结果：共对 35 个相关病例对照研究进行了荟萃分析，包括 7 个细胞因子基因和 15 个 SNP。IL-17A 中的SNP （rs2275913、rs3748067）；IL-17 F (rs763780)；IL-12A (rs568408)；IL-12B (rs3212227)；TNFA（rs1800629，rs361525）; IL-1B (rs16944)；IL-6 (rs1800795)；IL-10 (rs1800896) 基因与宫颈癌风险增加有关。在荟萃分析的多态性和 SIL 之间没有观察到关联。附加生物信息学分析建议的可能的转录调控途径TNFA和IL-10的基因通过MZF1（TNFA -308 G> A和IL-10 - 1082A> G）和ZNF263（TNFA -238 G> A）的转录因子的结合。