本文選題：Meta分析　切入點(diǎn)：XPC　出處：《華中科技大學(xué)》2008年碩士論文　論文類型：學(xué)位論文

【摘要】： 目的和意義:探討多環(huán)芳烴(PAHs)環(huán)境外暴露致機(jī)體早期生物學(xué)損傷,以至最終發(fā)展為腫瘤過程中的危險(xiǎn)因素,進(jìn)一步揭示各種環(huán)境因子和基因間的復(fù)雜關(guān)系,為多環(huán)芳烴暴露致機(jī)體損傷的微觀危險(xiǎn)度評價(jià)提供方法和模式。 資料與方法:1. Meta分析:搜索PubMed,EMBASE和中國生物醫(yī)學(xué)(CBM)三個數(shù)據(jù)庫中關(guān)于XPC基因多態(tài)性(Lys~(939)Gln, PAT-/+,和Ala~(499)Val)和與吸煙相關(guān)的腫瘤的研究,共27篇已發(fā)表的文獻(xiàn)進(jìn)行meta分析。 2.選取我國東北某大型鋼鐵公司某焦?fàn)t廠焦?fàn)t工人166名(暴露組)和該廠職業(yè)衛(wèi)生研究所近3個月未去過焦化廠的69名醫(yī)護(hù)人員(對照組)作為研究對象,測定其尿1-羥基芘濃度,彗星尾距,外周血淋巴細(xì)胞微核率,以及細(xì)胞色素P4501A1、細(xì)胞色素P450 2E1、谷胱甘肽S轉(zhuǎn)移酶P1、環(huán)氧化物水化酶、XRCC1、ERCC2基因多態(tài)性。用通徑分析和BP神經(jīng)網(wǎng)絡(luò)模型分析各影響因素與遺傳損傷的關(guān)系。 結(jié)果:1. Meta分析:(1)Lys~(939)Gln基因多態(tài)性有14個研究共6797名病例和9018名對照,Lys/Gln基因型與癌癥總體合并OR=0.99 (95% CI,0.92-1.06),Gln/Gln基因型OR=1.16 (95% CI,1.05-1.28);分層分析,Gln/Gln基因型與肺癌合并OR=1.28 (95% CI,1.07-1.53),在亞洲人群組合并OR=1.21 (95% CI,1.03-1.43)。(2)對Ala~(499)Val基因多態(tài)性,10個研究共5581名病例和6351名對照,癌癥總體合并OR值分別為:Ala/Val基因型OR=0.94 (95% CI,0.84-1.06)(隨機(jī)效應(yīng)模型),Val/Val基因型OR=1.24 (95% CI,1.08-1.42)(固定效應(yīng)模型);分層分析,Val/Val基因型與膀胱癌合并OR=1.33 (95% CI,1.06-1.68),在高加索人,合并OR=1.41 (95% CI,1.16-1.71)。(3)PAT-/+基因多態(tài)性有16個研究共4514名病例和5538名對照, PAT+/-基因型OR = 0.98(95% CI,0.90-1.07),PAT+/+基因型OR = 1.03(95% CI,0.91-1.16)。(4)基因-吸煙交互作用分析顯示,在不吸煙者中,攜帶PAT+/+基因型者患腫瘤的危險(xiǎn)度增高(OR = 1.44,95%CI 1.02-2.05;Q檢驗(yàn)P = 0.766),而攜帶PAT-/+基因型的不吸煙者患腫瘤的危險(xiǎn)無顯著性增加(OR = 0.99,95% CI 0.77-1.26)。 2.通徑分析結(jié)果表明,焦?fàn)t暴露和吸煙均是尿1-OHP濃度的重要影響因素,模型決定系數(shù)為0.75;對彗星尾距有顯著影響的因素及其作用大小為:尿1-OHP濃度 XRCC1-exon9變異基因型ERCC2-exon10變異基因型XRCC1-exon6變異基因型,模型決定系數(shù)為0.22;對CBMN微核率有顯著影響的因素及其作用大小為:焦?fàn)t暴露尿1-OHP濃度年齡mEH3變異基因型ERCC2-exon10變異基因型XRCC1-exon6變異基因型,模型的決定系數(shù)為0.27。 3.所構(gòu)建的BP神經(jīng)網(wǎng)絡(luò)結(jié)構(gòu)為17-8-1,微核的各影響因素中MIV值最大的為焦?fàn)t暴露(0.0011),而其它影響相對較大的因素依次為,mEH3變異基因型,ERCC2-exon10變異基因型,XRCC1-exon10變異基因型,是否吸煙,其中mEH3變異基因型對微核起負(fù)作用。 結(jié)論:質(zhì)量良好的meta分析能在一定程度上彌補(bǔ)分子流行病學(xué)分析中樣本量不足所帶來的缺陷,得出更肯定的結(jié)論。XPC基因多態(tài)性在腫瘤的發(fā)生中有微弱的作用,并且存在基因與吸煙之間的交互作用。外源性因素,尤其是焦?fàn)t暴露在機(jī)體早期遺傳損傷中發(fā)揮著重要的作用,其作用大于基因型。通徑分析和神經(jīng)網(wǎng)絡(luò)模型能擔(dān)任流行病學(xué)中篩選疾病危險(xiǎn)因素的任務(wù)。
[Abstract]:Purpose: To investigate polycyclic aromatic hydrocarbons (PAHs) exposure to the environment of early biological body injury, and ultimately the development of risk factors in the process of tumor, to reveal the complex relationship between genes and environmental factors, for PAHs exposure injury induced by micro risk assessment method and model.
Materials and methods: 1. Meta analysis: search for PubMed, EMBASE and three databases of Chinese Biomedical Science (CBM), including XPC polymorphism (Lys~ (939) Gln, PAT-/+, Ala~ (499) Val) and smoking related tumors. A total of 27 published literatures were used for meta analysis.
2. from a large Steel Corp in the northeast of China in a coke oven and 166 workers (exposure group) and occupation health research the factory nearly 3 months has not been to the coking plant of 69 medical workers (control group) as the research object, the determination of urinary 1- hydroxypyrene concentrations, comet tail moment, micronucleus of peripheral blood lymphocytes and the rate of cytochrome P4501A1, cytochrome P450 2E1, glutathione S transferase P1, epoxide hydrolase, XRCC1, polymorphism of ERCC2 gene. By path analysis and BP neural network model to analyze the relationship between various factors and genetic damage.
Results: 1. Meta analysis: (1) Lys~ (939) Gln gene polymorphism in 14 studies with a total of 6797 cases and 9018 controls, Lys/Gln genotype and overall cancer with OR=0.99 (95% CI, 0.92-1.06), Gln/Gln genotype OR=1.16 (95% CI, 1.05-1.28); the stratified analysis, the genotype of Gln and Gln/ patients with OR=1.28 (95% CI, 1.07-1.53), in the Asian population and OR=1.21 combination (95% CI, 1.03-1.43). (2) Ala~ (499) Val gene polymorphism, 10 of a total of 5581 cases and 6351 controls, with overall cancer OR values were: Ala/Val genotype OR=0.94 (95% CI (0.84-1.06), random effects model), Val/Val genotype OR=1.24 (95% CI, 1.08-1.42) (fixed effect model); hierarchical analysis, Val/Val genotype and bladder cancer with OR=1.33 (95% CI, 1.06-1.68), in Caucasians, with OR=1.41 (95% CI, 1.16-1.71). (3) PAT-/+ gene polymorphism is 16 A Study of 4514 cases and 5538 Controls, PAT+/- genotype OR = 0.98 (95% CI, 0.90-1.07), PAT+/+ genotype OR = 1.03 (95% CI, 0.91-1.16). (4) gene smoking interaction analysis showed that in non-smokers, risk of carrying PAT+/+ genotype increased cancer (OR = 1.44,95%CI 1.02-2.05; Q test P = 0.766), and the PAT-/+ genotype of non-smokers cancer risk no significant increase (OR = 0.99,95% CI 0.77-1.26).
2. path analysis results showed that the coke oven exposure and smoking are important factors for the urinary concentration of 1-OHP, the model decision coefficient is 0.75; factors have significant influence on the size from the comet tail is: the concentration of urinary 1-OHP XRCC1-exon9 variant genotype ERCC2-exon10 genotype XRCC1-exon6 genotype, 0.22 factors model decision coefficient; the role and size have a significant impact on the CBMN micronucleus rate: exposure of coke oven urine 1-OHP concentration age mEH3 variant genotype ERCC2-exon10 genotype XRCC1-exon6 genotype, the determination coefficient of the model was 0.27.
The structure of BP neural network constructed by the 3. 17-8-1, the influence factors of micronucleus MIV value for coke oven exposure (0.0011) and the other, relatively large impact factors, mEH3 genotype, ERCC2-exon10 genotype, XRCC1-exon10 genotype, smoking, the mEH3 genotype plays a negative role on the micronucleus.
Conclusion: good quality meta analysis can make up the defect sample molecular epidemiology analysis shortage brought to a certain extent, concluded that.XPC gene polymorphism certainly has weak role in tumorigenesis, and there is interaction between gene and smoking for exogenous factors, especially in coke oven exposure the early genetic damage plays an important role, which is greater than the genotype. The path analysis and the neural network model can serve as risk factors for disease screening in epidemiology.

【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2008
【分類號】：R363

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