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Cytochrome P450 1A1 gene polymorphisms and cervical cancer risk: A systematic review and meta-analysis.

ABSTRACT: This meta-analysis aims to examine whether the MspI and Ile462Val polymorphisms of cytochrome P450 1A1 (CYP1A1) are associated with cervical cancer risk.Eligible case-control studies were identified dated until July 2017. Pooled odds ratios (ORs) were used to assess the strength of the association between the two variants and cervical cancer risk.Thirteen studies were eligible (2148 cases and 2252 controls) concerning MspI polymorphism and 8 studies were eligible (1466 cases and 1690 controls) for Ile462Val polymorphism. MspI polymorphism seemed to result in cervical cancer risk in any genetic model (C allele vs T allele: OR?=?1.44, 95% confidence interval [CI]?=?1.16-1.79; heterozygous model: OR?=?1.40, 95% CI?=?1.08-1.82; homozygous model: OR?=?2.22, 95% CI?=?1.48-3.33, dominant model: OR?=?1.50, 95% CI?=?1.14-1.98 and recessive model: OR?=?1.80, 95% CI?=?1.35-2.41); similar significantly increased risk was found among Caucasians and Asians. Ile462Val polymorphism was associated with elevated cervical cancer risk (Val allele vs Ile allele: OR?=?1.85, 95% CI?=?1.27-2.67; heterozygous model: OR?=?1.42, 95% CI?=?1.28-1.61; homozygous model: OR?=?2.94, 95% CI?=?1.15-7.54; dominant model: OR?=?2.00, 95% CI?=?1.33-3.00); this finding was replicated upon Caucasian population.This meta-analysis demonstrated that polymorphisms in MspI and Ile462Val of CYP1A1 were risk factors for developing cervical cancer.

SUBMITTER: Ding B

PROVIDER: S-EPMC5895380 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Cytochrome P450 1A1 gene polymorphisms and cervical cancer risk: A systematic review and meta-analysis.

Ding Bo B Sun Wei W Han Suping S Cai Yunlang Y Ren Mulan M Shen Yang Y

Medicine 20180301 13

<h4>Objective</h4>This meta-analysis aims to examine whether the MspI and Ile462Val polymorphisms of cytochrome P450 1A1 (CYP1A1) are associated with cervical cancer risk.<h4>Methods</h4>Eligible case-control studies were identified dated until July 2017. Pooled odds ratios (ORs) were used to assess the strength of the association between the two variants and cervical cancer risk.<h4>Results</h4>Thirteen studies were eligible (2148 cases and 2252 controls) concerning MspI polymorphism and 8 stud ...[more]

PMID: 29595663

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Project description:ObjectiveRegulation of single nucleotide polymorphisms (SNP) in micro-RNA (miRNA) on the host cells may be one of the most important factors influencing the occurrence of cervical cancer based on the prevalence of HPV infection and the development of cervical cancer. In order to explore the contribution of miRNA polymorphism to the occurrence and development of cervical cancer, we conducted an analytical study.MethodsWe selected the polymorphisms of three widely studied miRNAs (miRNA-146a rs2910164, miRNA-499 rs3746444, and miRNA-196a2 rs11614913). Then, we conducted a meta-analysis (for the first time) to investigate their susceptibility to cervical cancer. Case control studies on the correlation between these three miRNAs and cervical cancer susceptibility were investigated by searching on from Pubmed, The Cochrane Library, Embase, CBM, CNKI, Wanfang database, and VIP database. Basic characteristics were recorded and meta-analysis of the case studies was performed using the STATA 15.1 software.ResultsThe miRNA-146a rs2910164 mutation significantly reduced the risk of cervical cancer in both recessive model (OR = 0.804, 95% CI = 0.652-0.992, P = 0.042; CC vs. CG+GG) and allelic model (OR = 0.845, 95% CI = 0.721-0.991, P = 0.038; C vs. G). There was no significant correlation between miRNA-499 rs3746444 and the risk of cervical cancer. The miRNA-196a2 rs11614913 mutation was significantly associated with a reduced risk of cervical cancer in homozygous model (OR = 0.641, 95% CI = 0.447-0.919, P = 0.016; TT vs. CC), dominant model (OR = 0.795, 95% CI = 0.636-0.994, P = 0.045; CT+TT vs. CC), recessive model (OR = 0.698, 95% CI = 0.532-0.917, P = 0.01; TT vs. CC+CT), and allelic models (OR = 0.783, 95% CI = 0.643-0.954, P = 0.015, T vs. C).ConclusionIn summary, this meta-analysis shows that the mutant genotypes of miRNA-146a rs2910164 and miRNA-196a2 rs11614913 are associated with a reduced risk of cervical cancer. Therefore, they may be two gene regulatory points for the prevention of cervical cancer.Systematic review registrationPROSPERO registration number CRD42021270079.

Project description:BackgroundMembers of the cytochrome P450 1A family metabolize many procarcinogens such as polycyclicaromatic hydrocarbons and heterocyclic amines. Inactivation of these enzymes is a prerequisite for cancer prevention and treatment in certain cases. Mechanism-based inhibition (time and co-factor dependent) is an effective method for the inactivation of these enzymes. Our recent study on emodin analogs revealed an anthraquinone with ortho-methylarylamine moiety that exhibited timedependent inhibition of P450 enzymes 1A1 and 1A2.MethodsTo determine whether the amino group or the methyl group or both were responsible for the time-dependent inhibition of these enzymes, a set of eleven compounds containing the orthomethylarylamine moiety were identified through a database search, and studied for the inhibition of the P450 enzymes 1A1, 1A2, 2A6 and 2B1. Our earlier studies on carbazole derivatives provided us with highly selective P450 1A2 inhibitors. Glycine scanning studies were performed on the docked proteinligand complexes of compounds 1-20 in order to understand the contribution of different protein residues towards the ligand binding.ResultsFour compounds were found to cause selective time-dependent inhibition of P450 1A1 with KI values ranging from 0.24 to 8.25 mM. These compounds exhibited only direct inhibition of P450 1A2. Molecular modeling studies of these molecules indicated that the shapes of the molecules, their binding modes, and the methyl substituent in close proximity (4.5-5.7 Å) to the heme-Fe all contributed to their selective time-dependent inhibition activity on P450 1A1. Glycine scanning studies for P450 1A1 indicated that ligand interaction with Phe123 was the strongest binding contributor and similar studies for P450 1A2 indicated that ligand interactions with the phenylalanine residues 226 and 260 were the largest binding contributors.ConclusionFour compounds have been identified that exhibit selective time-dependent inhibition of P450 1A1. Modeling studies have indicated that the proximity of the aromatic methyl group to the heme-Fe could be the main contributor for time-dependent inhibition. Future studies will focus on the confirmation of the involvement of the aromatic methyl group in enzyme inactivation.

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Cytochrome P450 1A1 gene polymorphisms and cervical cancer risk: A systematic review and meta-analysis.

Publications

Cytochrome P450 1A1 gene polymorphisms and cervical cancer risk: A systematic review and meta-analysis.

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