Genetic polymorphism associated with cervical cancer: a systematic review

Abstract

Introduction. Cervical cancer (CC) is one of the most common cancers in women. The CC etiological agent is the high-risk oncogenic human papillomavirus. In the meantime, not all women infected with this virus can develop cancer, thus suggesting that there is genetic predisposition to CC.The aim of the study was to analyze information about single nucleotide polymorphisms associated with the CC risk.Materials and methods. The performed search was focused on genome-wide association studies (GWAS) and meta-analyses conducted over the last 10 years and addressing the genetic risk of CC in the Caucasian population.Results. The most significant associations with CC were found in the following single nucleotide polymorphisms. Based on the GWAS data, they involve risk alleles rs138446575-T (OR = 2.39) TTC34; rs73728618-T (OR = 1.48) HLA-DQA1; rs3130196-C (OR = 1.4) HLA-DPB1; rs2516448-T (OR = 1.39 and 1.44) MICA and protective alleles rs9271898-A (OR = 0.64) and 9272143-C (OR = 0.65) between HLA-DRB1 and HLA-DQA1, rs55986091-A HLADQB1 (OR = 0.66). Based on the meta-analysis data, they involve genotype rs4646903-СС (OR = 4.65) CYP1A1 and protective alleles rs1801133-T (OR = 0.77) MTHFR, rs2333227-AA (OR = 0.57) MPO.Conclusion. The obtained data are critically important for development of laboratory techniques and reagent kits allowing for a personalized approach to identification of risk groups, which could benefit from compulsory vaccination and screening for pre-cancers of the cervix.

The genetic variant rs55986091 HLA-DQB1 is associated with a protective effect against cervical cancer

“…Future research plans involve investigating the underlying mechanisms by measuring the expression level of HLA-DQB1 in individuals with different genotype variants. Additionally, testing other SNPs that have shown statistically significant results in previous studies will be pursued ( 9 ). The data obtained from these studies will help in the creation of an analytical algorithm based on machine learning for calculating individual relative risks, further improving risk assessment and personalized management strategies for CC.…”

“…For other populations, the analysis demonstrated an OR of 2, with a 95% CI of 1.33-3 ( 14 ). In the analysis conducted on the European population (white population of Europe and the United States), a positive trend in CC development was observed, with an OR of 2.22 and a 95% CI of 1.48-3.33 ( 9 ). The rs1048943 SNP causes an amino acid substitution in the CYP1A1 gene, resulting in reduced enzymatic activity and being associated with the development of other types of cancers ( 14 , 15 ).…”

“…In our previous study, we conducted an analysis of SNPs associated with CC risk derived from genome-wide association studies (GWAS) and case-control studies, including a meta-analysis ( 9 ). For this particular publication, we focused on examining four specific SNPs: rs55986091 in HLA-DQB1 , rs138446575 in TTC34 , rs1048943 in CYP1A1 , and rs2910164 in miRNA-146a .…”