Cervical Cancer Genetic Susceptibility: A Systematic Review and Meta-Analyses of Recent Evidence

Abstract

IntroductionCervical cancer (CC) has one of the highest mortality rates among women worldwide. Several efforts have been made to identify the genetic susceptibility factors underlying CC development. However, only a few polymorphisms have shown consistency among studies.Materials and MethodsWe conducted a systematic review of all recent case-control studies focused on the evaluation of single nucleotide polymorphisms (SNPs) and CC risk, stringently following the “PRISMA” statement recommendations. The MEDLINE data base was used for the search. A total of 100 case-control studies were included in the meta-analysis. Polymorphisms that had more than two reports were meta-analyzed by fixed or random models according to the heterogeneity presented among studies.ResultsWe found significant negative association between the dominant inheritance model of p21 rs1801270 polymorphism (C/A+A/A) and CC (pooled OR = 0.76; 95%CI: 0.63–0.91; p<0.01). We also found a negative association with the rs2048718 BRIP1 polymorphism dominant inheritance model (T/C+C/C) and CC (pooled OR = 0.83; 95%CI: 0.70–0.98; p = 0.03), as well as with the rs11079454 BRIP1 polymorphism recessive inheritance model and CC (pooled OR = 0.79; 95%CI: 0.63–0.99; p = 0.04). Interestingly, we observed a strong tendency of the meta-analyzed studies to be of Asiatic origin (67%). We also found a significant low representation of African populations (4%).ConclusionsOur results provide evidence of the negative association of p21 rs1801270 polymorphism, as well as BRIP1 rs2048718 and rs11079454 polymorphisms, with CC risk. This study suggests the urgent need for more replication studies focused on GWAS identified CC susceptibility variants, in order to reveal the most informative genetic susceptibility markers for CC across different populations.

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

“…Genome-wide association studies identified cervical cancer susceptibility variants across different populations [23]. Therefore, the input of these and other polymorphic variants, may reflect the interindividuality of response in women with cervical cancer.…”

The effect of TP53 and P21 gene polymorphisms on papillary thyroid carcinoma susceptibility and clinical/pathological features

“…p21 is the major downstream effector of p53, which can act as a mediator between p53, DNA damage and repair and cell‐cycle inhibition . Due to the complex function of p21, p21 exhibits both tumor suppressor and oncogenic attributes . Several studies have been reported the effects of P21 polymorphisms on the function of its protein and may contribute to cancer susceptibility .…”

Genetic Susceptibility for Cervical Cancer in African Populations: What Are the Host Genetic Drivers?

“…To date, over 30 genes have been studied for their role in cervical cancer risk and these include, Bid, BRIP1, Caspase 8, CCR2, CTLA4, CYP1A1, EXO1, FASLG, FASR, HOTAIR, IFN gamma, PARP1, XRCC1, MDM2, IL10, IL12, HLA B/C, MTHFR, Tap2, TNF-a, TLR9, p16, PIK3CA, p21, and p53 Martínez-Nava et al, 2016;Mehta et al, 2015;Mei et al, 2014;Dos Santos et al, 2016;Sousa et al, 2011;Tsakogiannis et al, 2017;and Wang et al, 2017). Of these, genes only nine have been researched in African populations, highlighting a big gap in cervical cancer molecular epidemiology studies in a continent where 90% of the cervical cancer-related deaths are predicted (MboubaBouassa et al, 2017).…”

“…While these other factors increase the risk of developing cervical cancer, high-risk HPV (hr-HPV) subtypes have been identified as the only definitive etiological factor for cervical intraepithelial neoplasia (CIN) and cervical cancer (Martínez-Nava et al, 2016). HPV deoxyribonucleic acid (DNA) encodes three oncoproteins E5, E6, and E7 that deregulate the function of major histocompatibility complex I, p53, and retinoblastoma (Di Maio and Petti, 2013;Tomaic, 2016).…”

“…Current reports show the involvement of Caspase 8, CCR2, CTLA4, CYP1A1, EXO1, FASLG, FASR, HOTAIR, IFN gamma, PARP1, XRCC1, MDM2, IL10, IL12, HLA B/C, MTHFR, Tap2, TNF-a, TLR9, p16, PIK3CA, and p21 in cervical susceptibility (Alanazi et al, 2013;Barbisan et al, 2012;Chang et al, 2015;Jin et al, 2017;Ma et al, 2013;Martínez-Nava et al, 2016;Mehta et al, 2015;Mei et al, 2014;Piccolo and Crispi, 2012;Roszack et al, 2014;Dos Santos et al, 2016;Sousa et al, 2011;Tsakogiannis et al, 2017;Wang et al, 2017;and Zhuo et al, 2014). However, these findings have mostly been corroborated in Caucasian and Asian populations, and only a few have been reported on African populations.…”