【作者】 陈道俊；

【导师】 叶冬青；

【作者基本信息】 安徽医科大学 ， 流行病与卫生统计学， 2007， 硕士

【摘要】 目的探讨安徽滁州地区胃癌发生的危险因素,研究NQO1基因C609T和XRCC1基因G28152A位点多态性与滁州地区胃癌易感性的关系,及两基因的多态性与环境因素的交互作用对胃癌发生的影响,进一步揭示当地胃癌高发的可能原因,从而为采取有效的防治措施提供科学依据。方法采用以医院为基础的1:1配对病例对照研究,病例来自于四所滁州地市级医院经病理确诊为胃癌的新发病例,共112例。对照选择与病例在民族、性别、同居住地和年龄差别不小于5岁同期入院的无消化系统疾病、无肿瘤病人员,共112例。采用统一编制的调查表,由经过培训的调查员以直接询问的方式调查病例和对照。抽取病例和对照外周静脉血4～5ml,分离血清,运用常规的盐析法提取细胞中的基因组DNA。运用PCR-RFLP方法测基因型。采用条件Logistic回归模型对资料进行单因素分析、多因素分析和基因-环境交互作用分析,计算OR值及其95%CI等,所有数据分析采用SPSS11.0软件。结果1、环境因素与胃癌的研究结果显示:多因素Logistic回归分析后,滁州地区人群胃癌发生的主要危险因素有:日均吸烟支数(p = 0.001,OR=4.170,OR 95%CI=1.514～11.491)、食用熏烤食品(p = 0.001,OR=11.379,OR 95%CI=1.668～77.672)、年均施农药天数(p = 0.001,OR=9.494,OR 95%CI=1.289～69.920);而食用新鲜蔬菜(p = 0.000,OR=0.094,OR 95%CI=0.022～0.405)是胃癌的保护因素。2、基因因素与胃癌易感性的研究结果显示:NQO1 CC、CT、TT各基因型在病例组中分布分别为42.0%、25.0%、33.0%,在对照组中分别为50.9%、31.3%、17.8%,差异有统计学意义。携带NQO1TT基因型患胃癌OR值为2.261(p = 0.02,OR95%CI = 1.136~4.500),提示NQO1TT基因型增加了个体患胃癌的易感性。XRCC1 AA、AG、GG各基因型在病例组中分布分别为16.1%、33.0%、50.9%,在对照组中分别为17%、46.0%、38.0%,差异没有统计学意义,XRCC1 AG、GG基因型与胃癌的易感性无关。3、基因-环境因素交互作用研究结果显示:NQO1TT基因型与饮酒之间存在次相乘模型的正向交互作用(γ>1, OReg=3.142,OR 95% CI = 1.068~9.241);NQO1TT基因型与食用发黄米饭之间存在次相乘模型的负向交互作用(γ<1, OReg=4.302,OR95% CI = 1.126~16.427);NQO1TT基因型与食用腌制食品(>30斤/年)之间存在超相乘模型正向交互作用(γ>1, OReg=10.191,OR 95% CI = 1.778~58.398);NQO1TT基因型与食用水果(0次/周)之间存在超相乘模型的正向交互作用(γ>1, OReg=7.000,OR 95% CI = 1.167~42.000);NQO1TT基因型与食用新鲜蔬菜(<5次/周)之间存在超相乘模型的正向交互作用(γ>1, OReg=18.667,OR 95% CI = 3.497~99.635);NQO1TT基因型与饮茶(偶尔)之间存在次相乘模型的正向交互作用(γ>1, OReg=11.556,OR95% CI = 3.760~35.513);XRCC1 GG基因型与食用发黄米饭之间存在次相乘模型的正向交互作用(γ>1, OReg=4.800,OR 95% CI = 1.329~17.333);XRCC1 GG基因型与食用熏烤食品(>10斤/年)之间存在次相乘模型的正向交互作用(γ>1, OR eg=6.000,OR 95% CI = 1.082~33.274)。结论吸烟、饮酒、食用熏烤食品可以增加患胃癌的危险性;多食用新鲜蔬菜可以减少发生胃癌的几率;NQO1TT基因型增加了个体患胃癌的易感性;NQO1、XRCC1基因多态性及环境危险因素在胃癌发生中存在一定的交互作用。滁州地区胃癌的发生不仅与环境因素有关,而且与基因多态性有关。改变不良的行为习惯,采取科学的膳食结构可以有效的预防胃癌的发生。在NQO1TT基因型与胃癌的关系进一步证实之后,我们将可以考虑NQO1TT基因型作为胃癌的一级预防的筛检的指标之一。更多还原

【Abstract】 Objective:Epidemiological investigation was performed to study the co-effects of NQO1, XRCC1 genetic polymorphism, environmental exposure, and their interactions on the gastric cancer at Chuzhou region in Anhui province of PRC. Present research provides possible etiological concern on gastric cancer and promote further study interest.Methods:Individual epidemiological protocol was consisted with case-control study under the 1:1 subjects matched in local hospitals. The cases with the gastric cancer have been validated through histopathology .We studied 112 cases and 112 controls matched by gender, age, nationality and inhabited zone .Questionnaire were used to gathered individual information and the major environmental exposure data .Serum was obtained from 4-5 ml vein blood, following a simple salting out protocol to extract genomic DNA .Using the PCR-RFLP assay, we identified the genotype of NQO1 and XRCC1. Odds ratio (OR) which included the interaction risk factors between the gene and environmental exposure were determined using conditional logistic regression. Estimate of 95% confidence intervals (95%CI) was made. All analysis was performed with the SPSS Version 11.0(CDC, USA).Results1. After the simple and multi-variable statistical analysis ,we found some major risk factors from the environmental exposure; a lager increase in risk for daily smoking with the gastric cancer(p=0.001,OR=4.170,OR95%CI=1.514-11.491); baked food intake showing strong association with gastric cancer(p=0.001,OR=11.379,OR 95%CI=1.668-77.672); and a significant positive association was indicated between the pesticide utilization every year in local zone with the cancer(p=0.001,OR=9.494,OR 95%CI=1.289-69.920). However,association was showed between exposure and the cancer for the fresh vegetables intake(p=0.000.OR=0.094,OR95%CI=0.022-0.405), suggesting the vegetables was the protective factor for the gastric cancer.2. The distribution of genotype was significantly different in cases versus controls. The genotype frequency of NQO1 CC, CT , and TT was 42.0%,25.0%,and 33.0% in gastric cancer group respectively ,but which was 50.9%,31.3%,and 17.8% in controls respectively. Large increases in susceptibility found among whose genotype was NQO1 TT(p=0.02,OR=2.261,OR95T%CI=1.136-4.500). The different genotype of XRCC1, including AA, AG, and GG, showed no association with gastric caner when the frequency was calculated statistically.3. Interactions between genes and related exposure factors showed different effects on gastric caner. Significant positive-interaction was observed between NQO1 TT genotype and alcohol drinking (γ>1, OR=3.142, 95%=1.068~9.241), souse intake (γ>1, OR=10.191, 95%=1.778~58.398) which appeared to act in a super-multiplicative model. But the interaction of NQO1 TT genotype and mildewed rice intake (γ<1, OR=4.302, 95%=1.126~16.427) was significantly negative. Risk of the gastric cancer increased with the decreasing of fruit intake, fresh vegetables consumption, tea drinking. There was also obvious relationship between XRCC1 GG genotype and mildewed rice intake (γ>1, OR=4.800, 95%=1.329~17.333), baked food intake (γ>1, OR=6.000, 95%=1.082~33.274) showed significant positive-interaction and a sub- multiplicative model. ConclusionThe present study indicated that individual smoking, alcohol drinking, baked food intake increased the risk of gastric cancer, but more fresh vegetables consumption regulated down the incidence of gastric caner. After the genetic polymorphism investigation, the susceptibility to gastric cancer was regulated up by NQO1 TT genotype .Co-effects on gastric cancer were also found between the NQO1, XRCC1 and different environmental exposures. In general, incidence of the gastric cancer in Chuzhou could be effectively deceased when individuals taking the well-performed behaviors and valid dietary pattern. In addition, NQO1 TT genotype could be suggested as a index in early gastric cancer diagnosis.更多还原