A comprehensive meta-analysis of non-coding polymorphisms associated with precancerous lesions and cervical cancer

ObjectivesTo study the risk of polymorphisms present in the non-coding regions of genes related with cervical cancer.MethodsThe PubMed database was extensively searched using text-mining techniques to identify literature containing the association of single nucleotide polymorphisms and cervical cancer. Case-control studies published till June 2020 were considered for the meta-analysis if they fulfilled the selection criteria. The polymorphisms within each case-control study were checked for the presence of genotype data and then divided into groups based on the precancerous and cancerous conditions of the cervix. Odds ratio and 95% confidence intervals (CI) were used to study the effects of polymorphisms with the help of different genetic models (allele, dominant, recessive, heterozygous and homozygous). Also checked heterogeneity along with publication bias and statistical significance using the p-value.Results120 papers covering 48 unique non-coding SNPs having 37,123 cases and 39,641 control data was considered for the meta-analysis. The genotype data was categorised into Cancer, Precancer and “Cancer + Precancer” groups, for 43, 8 and 11 SNPs respectively. The meta-analysis identified 21 and 1 SNPs as significant in the Cancer and “Cancer + Precancer” groups. Among all the polymorphisms, rs1143627 (IL1B), rs1800795 (IL6), rs1800871 (IL10), rs568408 (IL12A), rs3312227 (IL12B), rs2275913 (IL17A), rs5742909 (CTLA4), rs1800629 (TNFα), and rs4646903 (CYP1A1) were found to increase risk of cervical cancer in at least three of the five genetic models.ConclusionWe identified potential non-coding SNPs corresponding to various cytokines like interleukins (ILs), tumor necrosis factor (TNF), interferon (IFN) and other immune related genes like toll like receptor (TLR), cytotoxic T-lymphocyte associated protein (CTLA) and matrix metalloproteinase (MMP), as significant with increased pooled OR in this meta-analysis pointing to risk association of the immune-related genes in cervical carcinogenesis.