摘要
目的:探讨肝癌高危人群中DNA氧化损伤与损伤修复酶基因多态性的关系。方法:收集广西扶绥县550例乙型肝炎病毒携带志愿者的外周血和尿样,应用高效液相-电化学法和聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)检测法检测肝癌高危人群的尿8-羟基-2-脱氧鸟苷(8-hydroxy-2-deoxy-guanosine,8-OHdG)水平和外周血中DNA损伤修复酶基因多态性,分析2者之间的关系。结果:肝癌高危人群中尿8-OHdG水平男性低于女性(P<0.01);PCR-RFLP检测法检测外周血DNA损伤修复酶X线修复交叉互补组1(X-ray repair cross com-plementing group 1,XRCC1)基因和人8-羟基鸟嘌呤DNA糖苷酶1(human 8-oxoguanine DNA glycosylase 1,hOGG1)基因多态性的结果发现,女性hOGG1 Ser326Ser和XRCC1 Arg194Arg者的尿8-OHdG水平较低(P=0.049,P=0.048)。将尿8-OHdG水平以中位数为基点分为高、低2组进行多因素分析发现,hOGG1突变型杂合子和突变型纯合子者的尿8-OHdG水平较高,尤其在女性研究对象中更明显(P<0.05)。结论:DNA损伤修复酶基因多态性可以影响其编码的蛋白质的功能,影响机体对损伤DNA的修复作用,最终可能导致肿瘤发生的个体差异。
Objective:To investigate the association of phenotypic oxidative DNA damage with polymorphism of DNA repair genes in a high-risk population of liver cancer.Methods:This study was carried out in Fusui County,Guangxi,China.A total of 550 healthy adults who were positive for hepatitis B surface antigen(HBsAg) were voluntarily recruited.Urinary level of 8-hydroxy-2-deoxy-guanosine(8-OHdG) was measured using high performance liguid chromatography-eletrochemical detection(HPLC-ECD).Genetic polymorphisms of DNA repair genes were identified by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The relationship between the level of 8-OHdG and the polymorphisms of DNA repair genes was analyzed.Results:In these individuals with high risk of developing liver cancer,male subjects had significantly lower urinary 8-OHdG levels than females(P<0.01).The polymorphism of 8-oxoguanine DNA glycosylase 1(hOGG-1) and X-ray repair cross complementing group 1(XRCC-1) was genotyped using PCR-RFLP.It discovered that female subjects genotyped as hOGG-1 Ser326Ser or XRCC-1 Arg194Arg had lower urinary 8-OHdG level than those with heterozygous or homozygous genotypes(P=0.049 and P=0.048).Based on the median level of 8-OHdG we divided subjects into two groups: high 8-OHdG group and low 8-OHdG group.Multivariate analysis showed that subjects with mutated heterozygous and mutated homozygous genotypes of hOGG-1 had significantly higher urinary 8-OHdG levels,especially in females(P<0.05).Conclusion:Polymorphisms of DNA repair genes influence the function of the encoded proteins and the DNA repair capability,thus inducing the individual difference of tumorigenesis.
出处
《肿瘤》
CAS
CSCD
北大核心
2010年第9期782-787,共6页
Tumor
