人AKR1C3基因多态性与癌症易感性关联的Meta分析

发布时间：2018-04-01 15:52

本文选题：AKR1C3　切入点：单核苷酸多态性　出处：《福建医科大学》2016年硕士论文

【摘要】：【背景】醛-酮还原酶(AKR)是氧化还原酶超家族的成员之一。它包含16个家族,约190个成员,广泛存在于各类生物体中。AKR1C3是醛酮还原酶第一个家族的C3成员。人类AKR1C3基因编码NADPH依赖型氧化还原酶,并催化醛酮化合物等致癌物质还原成相应的无毒或低毒的醇类,从而保护细胞不受损害。人AKR1C3基因具有高度多态性,这主要是因为AKR1C3基因中存在多个单核苷酸多态性(SNPs),AKR1C3基因多个位点的单核苷酸突变导致的其编码肽链氨基酸序列发生改变,从而影响酶蛋白结构及其催化解毒作用,而影响癌症易感性。既往研究表明AKR1C3基因单核苷酸多态性与肿瘤的发生和发展相关。目前国内外已经已有多项关于AKR1C3基因单核苷酸多态性与癌症易感性关联的研究,但是研究结果并不完全一致,因此我们进行这一Meta分析来综合地评估AKR1C3基因单核苷酸多态性与癌症易感性的相关性。【方法】检索PubMed、EMbase、OVID、CMB(中国生物医学数据库)和Cochrane library数据库。收集有关AKR1C3基因单核苷酸多态性与癌症易感性关系的文献,剔除不符合要求的文献。并根据异质性检验结果选择固定效应模型和随机效应模型进行数据合并分析。然后计算合计的比值比(OR)及95%可信区间来评估AKR1C3基因单核苷酸多态性与癌症相关性,并通过亚组分析探讨异质性来源,运用漏斗图评估发表偏倚,敏感性分析检验结果稳定性。【结果】本研究共纳入12篇文献,其中关于rs12529位点的8篇,关于rs4881400位点的3篇,关于rs2245191位点的4篇,关于rs3763676位点的3篇,以及关于rs12387位点的3篇,分析结果显示AKR1C3基因rs12529位点的单核苷酸多态性与癌症的易感性无显著关联,但亚组分析发现在亚洲人群中rs12529位点单核苷酸多态性在以下基因模型(等位基因模型G vs C,OR=1.64,95%CI 1.13 2.38,P=0.009;显性基因模型CG+GG vs CC,OR=1.78,95%CI 1.03 3.07,P=0.04)与癌症易感性明显相关。此外本研究还发现携带rs3763676位点GA或GG基因型个体相对AA基因型个体存在更高的癌症风险(显性基因模型GA+GG vs AA,OR=1.20,95%CI 1.03 1.40,P=0.02)。关于人AKR1C3 rs4881400、rs2245191和rs12387位点单核苷酸多态性分析结果,没有发现其与癌症易感性相关。【结论】人AKR1C3基因rs12529位点多态性可能与亚洲人癌症的易感性相关,携带G等位基因可能是癌症的危险因素。且发现携带AKR1C3基因rs3763676位点GA或GG基因型个体相对AA基因型个体其癌症易感性增高。AKR1C3基因rs4881400、rs2245191和rs12387位点不影响癌症的易感性。但上述结果仍需要更多大样本及高质量的研究来证实。
[Abstract]:Background: aldehyde-ketone reductase (AKR) is a member of the superfamily of redox enzymes.It consists of 16 families with about 190 members. AKR1C3 is the first C3 member of aldehydes and ketones reductase.Human AKR1C3 gene encodes NADPH dependent redox reductase and catalyzes the reduction of carcinogens such as aldehydes and ketones to corresponding nontoxic or low toxic alcohols so as to protect cells from damage.Human AKR1C3 gene is highly polymorphic, which is mainly due to the change of amino acid sequence of encoding peptide chain caused by multiple single nucleotide mutations in AKR1C3 gene.Thus affecting the enzyme protein structure and catalytic detoxification, and affect cancer susceptibility.Previous studies have shown that the single nucleotide polymorphism of AKR1C3 gene is associated with the occurrence and development of tumor.Therefore, we conducted this Meta analysis to evaluate the association between single nucleotide polymorphisms of AKR1C3 gene and cancer susceptibility. [methods] PubMedbase OVIDB (Chinese Biomedical Database) and Cochrane library database were searched.To collect the literature about the relationship between AKR1C3 gene single nucleotide polymorphism and cancer susceptibility, and eliminate the non-conforming literature.According to the results of heterogeneity test, fixed effect model and random effect model are selected for data merging analysis.Then we calculated the ratio ratio (ORR) and 95% confidence interval to evaluate the association between AKR1C3 gene single nucleotide polymorphism and cancer, and used subgroup analysis to explore the source of heterogeneity, and to use funnel graph to evaluate publication bias.[results] A total of 12 articles were included in this study, including 8 articles on rs12529 loci, 3 on rs4881400 loci, 4 on rs2245191 loci, 3 on rs3763676 loci, and 3 on rs12387 loci.The results showed that there was no significant association between the single nucleotide polymorphisms at rs12529 locus of AKR1C3 gene and the susceptibility to cancer.In addition, it was also found that individuals with rs3763676 locus GA or GG genotype had a higher cancer risk than AA genotype individuals (dominant gene model GA GG vs AA GG 1.20 95 / 1.03 CI 1.40 P0. 02).The results of single nucleotide polymorphism analysis of human AKR1C3 rs4881400 rs2245191 and rs12387 locus showed no association with cancer susceptibility. [conclusion] the polymorphism of rs12529 locus of human AKR1C3 gene may be associated with cancer susceptibility in Asian people.Carrying the G allele may be a risk factor for cancer.It was also found that the individuals carrying rs3763676 locus of AKR1C3 gene GA or GG genotype were more susceptible to cancer than those of AA genotype. Rs4881400 rs2245191 and rs12387 locus of AKR1C3 gene did not affect the susceptibility to cancer.But these results still need more large samples and high-quality research to confirm.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R730.2

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