【作者】 宋韶芳；

【导师】 陈思东；

【作者基本信息】 广东药学院 ， 病原生物学， 2008， 硕士

【摘要】 在2006年全国第三次死因回顾性抽样调查中发现,癌症是广东省顺德区居民的首位死因,而肝癌死亡率居癌症死因顺位的第一位。2004-2005年顺德肝癌死亡率49.84/10万,超过全国死亡水平。肝癌潜在减寿年数(PYLL)占恶性肿瘤38.60%,该区居民去除肝癌后寿命可延长1.21岁,肝癌正严重威胁着该区居民的生命。目前有关顺德区肝癌的流行病学研究较少,人们对肝癌高发的主要危险因素尚不清楚,因此对顺德区肝癌进行流行病学调查,探索危险因素有重要意义。研究目的:通过1:1匹配的病例对照研究,探讨顺德区肝癌的危险因素;研究肿瘤坏死因子(TNF)α-308位点基因多态与肝癌遗传易感性的关系,以及TNF-α-308位点基因多态与环境因素在肝癌发生中的交互作用;分析肝癌患者的出生顺序初步了解环境因素与遗传因素在该区肝癌发生中的相对作用。对象与方法:研究对象来源于顺德区医院2004-2007年住院的并在该区居住10年及以上,顺德籍肝癌新发病例及同胞。对照按照1:1匹配的方法收集,要求其未患肝癌,在该区居住10年及以上、与病人同村、同性别、年龄与病例诊断年龄±3岁,无血缘关系。相关测量包括:(1)问卷调查:调查对象的一般人口学特征、吸烟史、饮酒史、食物摄入情况、饮水状况、相关疾病史,出生顺序等。(2)实验室检测:○1用酶联免疫吸附试验(ELISA)检测HBV感染五项指标、甲胎蛋白、丙肝抗体、肝吸虫抗体。○2用聚合酶链反应-限制片段长度多态性方法(PCR-RELP)分析TNF-α-308位点。先应用条件Logistic回归模型分析吸烟、饮酒、TNF-α-308基因多态等因素与肝癌的关系和它们之间的交互作用,然后对肝癌患者的出生顺序进行初步分析。结果:共调查病例对照81对,病例同胞共计368人(含病例),其中有肝癌患者89人。采集病例对照血样78对,其中男性70对,女性8对。(1)应用1:1匹配的病例对照研究方法,发现TNF2等位基因在病例组和对照组的分布差异有统计学意义(P=0.012),OR值为2.67(95%CI:1.24一5.74)。(2)应用条件Logistic回归模型分析顺德区肝癌的危险因素,发现HBsAg、肝病史、饮酒量是肝癌发生的主要危险因素。(3)HBsAg与TNF2等位基因存在交互作用:其OR值为19.83(95%CI:4.20-93.61);超相对危险比(RERI)为2.22,交互作用归因比(API)为0.29,两因素交互作用指数(SI)为1.50。(4)肝病史与TNF2等位基因存在交互作用:其OR值为7.63(95%CI:1.05-67.71);其RERI为2.22,API为0.29,SI为1.50。(5)饮酒与TNF2等位基因存在交互作用:其OR值为4.57(95%CI:1.62-12.88);其RERI为1.39,API为0.30,SI为1.63。(6)HBsAg(+)组肝癌发生与出生顺序有关;而HBsAg(-)组肝癌发生与出生顺序无关。结论:(1)TNF-α-308基因多态与肝癌有关联,TNF2等位基因可能是肝癌的遗传易感基因。(2)应用1:1匹配的病例对照研究方法探讨顺德区居民肝癌危险因素,发现HBsAg、饮酒量、肝病史是肝癌发生的主要环境危险因素。(3)HBsAg、饮酒、肝病史与TNF2等位基因存在交互作用。(4)肝癌患者出生顺序分析提示HBV感染是顺德区肝癌发生的重要环境因素,控制HBV感染后,遗传因素对该区肝癌发生的作用不容忽视。更多还原

【Abstract】 It was reported that cancer was in the first place of the death causes in Shunde, Guangdong and primary liver cancer (PLC) mortality was the first in Cancer from the Third Time of Nationwide Death Cause Sample Survey in 2006.PLC mortality was 49.84/1,000,000 above national average in Shunde in 2005.PYLL of PLC occupied cancer 38.60%.removed PLC,the resident can live 1.21 years longer.The people was severity threaten by PLC. But the studies on epidemiology of Primary Live Cancer in Shunde were seldom reported. The risk factors of PLC were not identify .So, it was necessary explore risk factors of PLC in Shunde City and this work had a certain realistic significance.Purposes:To performed a case-control study to explore risk factors of PLC, to research the association between genetic polymorphisms of the human tumor necrosis factor-α-308 position and susceptibility to PLC, and to probe the interaction between environmental and genetic factors in hepatocarcinogenesis by applying molecular biological technology .To analyse the birth orders of PLC cases, trying to know the relative roles of environmental and genetic factors in Hepatocarcinogenesis.Objects and methods:Subjects were PLC patient in hospital from 2004 to 2007 and sibling who lived in Shunde above 10 years. The controls who didn’t have PLC, not blood relation with patient at the same village, same sex, age±3 years, living in Shunde above 10 years.The contents of survey include:(1) Questionnaire: general conditions;personal history of smoking, drinking,eating, drink water,disease status, birth order, etc;(2)Laboratory examination:○1 to detect HBV, HCV,AFP, liver fluke by ELISA .○2 to analyze TNF-α-308 position by PCR-RELP.We first applied conditional logistic regression analysis to explore the main effects and interactional effects of HBV, smoking, drinking,TNF2in hepatocarcinogenesis. Then we analyzed the birth orders of PLC cases.Results:(1) The frequencies of allele TNF2 were significant differences between case group and control group (P=0.012), with the OR of 2.67 (95%CI: 1.24-5.74).(2) Applied conditional logistic regression to explore risk factors of PLC , Hepatitis B, alcohol consumption, liver desease history were associated with increased risks of PLC in this study.(3) HBsAg was interacted with the TNF2 allele during the generation of PLC, With the OR=19.83(95%CI:4.20-93.61); their RERI were 14.39, their API were 0.7253,their SI were 4.23.(4) Liver desease history was interacted with the TNF2 allele during the generation of PLC, With the OR=7.63(95 %CI:1.05-67.71),their RERI were 2.22, their API were 0.29,their SI were 1.50.(5) Alcohol consumption was interacted with the TNF2 allele during the generation of PLC, With the OR=4.57(95 %CI:1.62-12.88),their RERI were 1.39, their API were 0.30,their SI were 1.63. (6) No relation was found between birth order and pathogenesis of PLC in the patient of HBsAg (-),but in the patient of HBsAg(+) birth order had relation with pathogenesis of PLC.Conclusion:(1) There was association between genetic polymorphisms of the human tumor necrosis factor-α-308 position and PLC; the TNF2 allele was susceptibility to PLC.(2) Applied conditional logistic regression to explore risk factors of PLC , Hepatitis B, alcohol consumption, liver desease history were associated with increased risks of PLC in this study.(3) The TNF2 allele was interacted with HBsAg, liver desease history, alc-ohol consumption.(4) Hepatitis B played more important role than genetic factors in hepatica-rcinogenes in Shunde.But control Hepatitis B, genetic factors would play important role in hepatocarcinogenesis .更多还原