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肺癌发病常见危险因素的临床病例对照分析及XPD基因作用的初探

发布时间:2018-09-14 08:44
【摘要】:肺癌近几年已成为严重危害人类健康的疾病,其死亡率在全球各国均上升显著,在我国已跃居肿瘤死因首位。肺癌的预防及后续诊治是当前极为重要的公共健康问题之一。流行病学研究报道了肺癌的几种常见的危险因素,包括吸烟史,疾病史及易感基因,我们将从生活行为方式、精神心理因素、职业环境因素、饮食因素、既往有无呼吸系统疾病史及家族性肿瘤病史等方面入手进行分析总结,期望为肺癌的防控提供理论依据。同时本文还重点强调了易感基因的独特作用,通过meta分析的方法更进一步分析肺癌易感基因与肺癌的关联性。第一部分常见肺癌危险因素的病例对照分析目的:探讨影响原发性肺癌的常见的危险因素,为阐明肺癌病因提供依据。方法:应用病例对照研究的方法,收集北京军区总医院2014-2016年收治的126例肺癌患者,对照118人,统一采用问卷调查方法,对所有入选人群的一般情况(性别、年龄、体质指数)、生活行为方式(吸烟或被动吸烟情况、饮酒、饮茶、饮咖啡、熬夜)、精神心理因素、职业环境因素、饮食、既往有无呼吸系统疾病史及家族性肿瘤病史进行调查。所有结果均采用SPSS22.0统计软件包分析。结果:有长期吸烟行为及暴露于被动吸烟环境中的患者患肺癌的风险性显著增加,其OR值分别是1.341和1.196;不适当的饮酒行为及长期睡眠不足患肺癌的风险增加1.828和2.04倍;经历不和谐的婚姻、生活压力大和长期精神压抑的人群易患肺癌,情绪自我调节能力差或生活态度消极也可增加肺癌发生的风险,其OR值分别为3.581和1.613;与苯、石棉、金属粉尘、煤尘和油烟燃料接触增加肺癌患病的发生率;摄入较多的新鲜果蔬和鱼肉,多食用大蒜等是肺癌的保护性因素,而进食过多腌渍食品则会增加3.073倍肺癌的患病风险;肺结核病史、COPD病史等肺部疾病与肺癌均存在统计学关联,有肿瘤家族史的研究对象患肺癌的风险增加10.049倍。结论:肺癌的发病与长期大量吸烟、被动吸烟、长期睡眠不足、生活态度消极悲观、长期精神压抑、接触石棉、金属粉尘、厨房燃料油烟、食用腌渍食品和长期慢性呼吸道疾病史(如肺结核、COPD疾病病史)等多种因素有关,因此应将特殊人群如将长期吸烟、精神压力大、长期暴露于有害物质、慢性肺结核、COPD人群或有肿瘤家族史的人群作为预防肺癌的重点人群。第二部分XPD基因遗传多态性与人群肺癌易感性关系的meta分析目的:DNA损伤修复基因XPD(Xeroderma Pigmentosum group D)参与核苷酸切除修复(Nucleotide Excision Repair,NER)过程,其单核苷酸多态性(SNP,single nucleotide polymorphism)的变异与肺癌易感性相关,因此本文通过meta分析的方法,系统评价核苷酸切除修复基因XPD多态性与肺癌的关联。方法:检索Pubmed、Embase、medline、中国生物医学文献数据库(CBM)、万方、维普、中国知网(CNKI)等中英文数据库的相关文献,检索时间设定为从建库至2016年3月,按照拟定的标准进行筛选。文献主要涉及ERCC2/XPD基因多态性Lys751Gln及Asp312Asn与肺癌易感性关系的病例对照研究。用Revman 5.2对入组研究进行Meta分析,同时行亚组分析。结果:截止2016年3月1日符合条件的文献共32篇,其中包含34项研究,累计病例数为19542人,对照组人数为25078人。Asn/Asn、Gln/Gln及Lys/Gln基因型携带者肺癌易感性明显升高(p0.05),提示与肺癌的发生的易感性显著相关。结论:ERCC2/XPD基因的单核苷酸多态性Asp312Asn和Lys751Gln作为肺癌发病的危险因素与肺癌易感性相关,尤其是等位基因Asn在亚洲人群中的作用、751Gln/Gln和751Lys/Gln基因在高加索及亚洲人群、医院及社区人群的肺癌发病风险增加。
[Abstract]:Lung cancer has become a serious disease endangering human health in recent years. The mortality rate of lung cancer has risen remarkably in all countries of the world and has ranked first in China. Prevention and follow-up treatment of lung cancer is one of the most important public health problems. Epidemiological studies have reported several common risk factors of lung cancer, including smoking history. History of disease and susceptibility genes will be analyzed and summarized from aspects of lifestyle, psychosocial factors, occupational environment factors, dietary factors, past history of respiratory diseases and familial oncology in order to provide theoretical basis for the prevention and control of lung cancer. The association between lung cancer susceptibility genes and lung cancer was further analyzed by meta-analysis. Part I: Case-control analysis of common lung cancer risk factors Objective: To explore the common risk factors affecting primary lung cancer and provide evidence for elucidating the etiology of lung cancer. A total of 126 lung cancer patients admitted to our hospital from 2014 to 2016 were compared with 118 controls. Questionnaires were used to investigate the general situation (sex, age, body mass index), lifestyle (smoking or passive smoking, drinking alcohol, tea, coffee, staying up late), psychosocial factors, occupational environment, diet, and previous respiratory system of all the selected people. Results: Patients with long-term smoking and exposure to passive smoking had a significantly increased risk of lung cancer, with OR values of 1.341 and 1.196 respectively; those with inappropriate drinking and chronic sleep deprivation had a significantly increased risk of lung cancer. The OR value of lung cancer was 3.581 and 1.613 respectively, and exposure to benzene, asbestos, metal dust, coal dust and soot fuels increased the incidence of lung cancer. Increasing intake of fresh fruits, vegetables, fish and garlic was the protective factor for lung cancer, while eating too much pickled food increased the risk of lung cancer by 3.073 times. Pulmonary diseases such as tuberculosis, COPD and other lung diseases were statistically associated with lung cancer, with a 10.049-fold increase in the risk of lung cancer among subjects with a family history of cancer. Conclusion: The incidence of lung cancer is related to many factors, such as long-term smoking, passive smoking, long-term sleep deprivation, negative and pessimistic attitude towards life, long-term mental depression, exposure to asbestos, metal dust, cooking fumes, eating pickled food and long-term history of chronic respiratory diseases (such as tuberculosis, COPD) and so on. Long-term smoking, high mental stress, long-term exposure to harmful substances, chronic tuberculosis, COPD, or family history of cancer as the focus of the population to prevent lung cancer. Part II: XPD gene genetic polymorphisms and population susceptibility to lung cancer meta-analysis Objective: DNA damage repair gene XPD (Xeroderma Pigmentosum group D) involved in nuclear Nucleotide Excision Repair (NER) process, its single nucleotide polymorphism (SNP) mutation and lung cancer susceptibility related, so this paper through meta-analysis method, systematic evaluation of nucleotide excision repair gene XPD polymorphism and lung cancer association.Methods: Retrieve Pubmed, Embase, medline, in. Chinese and English databases, such as CBM, Wanfang, Weipu, CNKI, were selected according to the established criteria from the date of establishment to March 2016. The literature mainly involved case-control studies on the relationship between ERCC2/XPD gene polymorphism Lys751Gln and Asp312Asn and susceptibility to lung cancer. Results: As of March 1, 2016, there were 32 eligible literatures, including 34 studies, with a cumulative number of cases, and 25 078 controls. Asn/Asn, Gln/Gln and Lys/Gln genotype carriers were significantly more susceptible to lung cancer (p0.05). Conclusion: Single nucleotide polymorphisms of ERCC2/XPD gene Asp312Asn and Lys751Gln are associated with lung cancer susceptibility as risk factors for lung cancer, especially the role of allele Asn in Asian population, 751Gln/Gln and 751Lys/Gln genes in Caucasian and Asian populations, hospitals and community populations. The risk is increased.
【学位授予单位】:大连医科大学
【学位级别】:硕士
【学位授予年份】:2016
【分类号】:R734.2

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1 金珊珊;肺癌发病常见危险因素的临床病例对照分析及XPD基因作用的初探[D];大连医科大学;2016年



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