Association between genetic polymorphisms of DNA base excision repair genes and evolution of precancerous gastric lesions in a Chinese population
Association between genetic polymorphisms of DNA base excision repair genes and evolution of precancerous gastric lesions in a Chinese population
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DNA碱基切除修复基因多态性与中国人群胃癌前病变演变的关系
DOI：
10.1093/carcin/bgp018
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发表时间：
2009-03-01
期刊：
影响因子：
4.7
通讯作者：
You, Wei-Cheng
中科院分区：
文献类型：
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作者：
Li, Wen-Qing;Zhang, Lian;You, Wei-Cheng
碱基切除修复途径可能在幽门螺杆菌致炎相关DNA损伤修复中发挥重要作用。目的探讨X线修复交叉互补基因1（XRCR 1）多态性与乳腺癌发病的相关性（XRCC 1，Arg 194 Trp和Arg 399 Gln），腺苷二磷酸核糖基转移酶（ADPRT，Val 762 Ala），8-氧代鸟嘌呤DNA糖基化酶（OGG 1，Ser 326 Cys）和脱嘌呤/脱嘧啶核酸内切酶1本研究在中国胃癌高发区临朐县开展了一项以人群为基础的队列研究，旨在探讨幽门螺杆菌（H. pylori）相关性胃癌前病变与APE 1（Asp 148 Glu）的关系。采用聚合酶链反应（PCR）-变性高效液相色谱法和PCR-限制性片段长度多态性分析法对1281例幽门螺杆菌感染者进行基因型测定。我们发现，携带XRCC 1 - 194 Arg/Trp+Trp/Trp联合基因型的受试者胃病变消退的机会增加[校正比值比（OR）= 1.44; 95%置信区间（CI）= 1.06-1.96]，而携带XRCC 1 - 399 Arg/Gln+Gln/Gln基因型的受试者胃病变消退的机会减少（OR = 0.68; 95%CI = 0.49-0.92）。分层分析表明，在携带XRCC 1 - 399 Arg/Gln+Gln/Gln基因型的受试者中观察到进展风险增加OR = 1.60; 95%CI = 1.09-2.36）或OGG 1 - 326 Ser/Cys+Cys/Cys基因型（OR = 1.95; 95%CI = 1.03-3.71）基线时肠上皮化生或异型增生或携带XRCC 1 - 399 Arg/Gln+Gln/Gln基因型和吸烟（OR = 1.58; 95%CI = 1.02-2.45）。携带XRCC 1 -399或OGG 1 -326中一种或两种危险基因型的受试者的疾病进展风险显著增加，OR分别为2.83（95%CI = 1.32-6.08）、2.22（95%CI = 1.24-3.98）和2.27（95%CI = 1.26-4.10）。提示XRCC 1-Arg 194 Trp、XRCC 1-Arg 399 Gln和OGG 1-Ser 326 Cys基因多态性可能在幽门螺杆菌相关性胃黏膜病变的发生发展中起重要作用。
Base excision repair pathway may play an important role in repairing DNA damage related to Helicobacter pylori-induced inflammatory process. To evaluate the association between genetic polymorphisms of X-ray repair cross-complementing group 1 (XRCC1, Arg194Trp and Arg399Gln), adenosine diphosphate ribosyl transferase (ADPRT, Val762Ala), 8-oxoguanine DNA glycosylase (OGG1, Ser326Cys) and apurinic/apyrimidinic endonuclease 1 (APE1, Asp148Glu) and evolution of H.pylori-associated precancerous gastric lesions, a population-based cohort study was conducted in Linqu County, a high-risk area of gastric cancer in China. Genotypes were determined by polymerase chain reaction (PCR)-based denaturing high-performance liquid chromatography and PCR-restriction fragment length polymorphism analysis in 1281 H.pylori-infected subjects. We found that subjects carrying the combined XRCC1-194Arg/Trp+Trp/Trp genotype had an elevated chance of regression of gastric lesions [adjusted odds ratio (OR) = 1.44; 95% confidence interval (CI) = 1.06-1.96], whereas subjects carrying the XRCC1-399Arg/Gln+Gln/Gln genotype had a decreased chance of regression (OR = 0.68; 95% CI = 0.49-0.92). Stratified analysis indicated that an increased risk of progression was observed in subjects carrying the XRCC1-399Arg/Gln+Gln/Gln genotype (OR = 1.60; 95% CI = 1.09-2.36) or OGG1-326Ser/Cys+Cys/Cys genotype (OR = 1.95; 95% CI = 1.03-3.71) with intestinal metaplasia or dysplasia at baseline or carrying the XRCC1-399Arg/Gln+Gln/Gln genotype and smoking (OR = 1.58; 95% CI = 1.02-2.45). Furthermore, a significantly increased risk of progression was observed in subjects carrying one or two hazard genotypes of XRCC1-399 or OGG1-326, the OR was 2.83 (95% CI = 1.32-6.08), 2.22 (95% CI = 1.24-3.98) or 2.27 (95% CI = 1.26-4.10), respectively. These findings suggest that genetic polymorphisms in XRCC1-Arg194Trp, XRCC1-Arg399Gln and OGG1-Ser326Cys may play important roles in the evolution of H.pylori-associated gastric lesions in this high-risk population.