胃癌和胃溃疡组织中ERβ与hPOT1基因单核苷酸多态性相关性(崔)

1我的意见：乱！没有条理，不如拆开了，写成两篇，一篇写雌激素受体，一篇写Hp0T1。胃癌和胃溃疡组织中ERβ与hPOT1基因单核苷酸多态性相关性钱春野1杨留才1周娟1宋署21盐城卫生职业技术学院2盐城市第一人民医院（江苏盐城224006）*[基金项目]2008年盐城市医学科技发展计划项目（项目编号2008121）[摘要]目的：研究胃癌和胃溃疡组织中ERβ与hPOT1基因单核苷酸多态性相关性。方法：以100例原发性胃癌为实验组，90例胃溃疡为对照组，免疫组织化学SP法检测ER-和hPOT1蛋白，RT-PCR法检测ERβCA重复序列多态性和G1082A多态性以及hPOT1基因单核苷酸多态性。结果：ER-在实验组和对照组的阳性表达率依次为68.0%和23.3%，而POT1的阳性率分别为86.0%和1.1%,，差异均具有显著性(P0.01)。其中分化程度低、浸润深的、有淋巴结转移和五年死亡者ERβ和POT1阳性率分别高于分化程度高、浸润浅的、无淋巴结转移和五年生存者，且临床分期处于Ⅰ、Ⅱ期者ERβ阳性率显著低于Ⅲ期者(P0.01/0.05)。而ERβ和POT1的阳性表达与初复发、年龄、肿瘤大小和组织学类型无关（P0.05），并随着基因表达阳性率增加，患者发生远处转移危险度增加(P0.001)，患者5年存活率下降(P0.05)。ERβ基因CA重复序列对照组和实验组基因型分布均符合Hardy-Weinberg平衡(P0.05)，两组基因型SS、SL、LL分布的比较差异无统计学意义(P0.05)，两组等位基因S、L频率的比较差异亦无统计学意义(P0.05)，提示ERβ基因的CA重复序列多态性表达与胃癌发病无关联。ERβG1082A多态性中，RsaⅠ多态性分析：实验组和对照组均符合Hardy-Weinberg遗传平衡定律(P0.05)。两组基因型rr、Rr、RR分布的比较差异无统计学意义(P0.05)，两组等位基因r、R频率的比较差异亦无统计学意义(P0.05)；ERβAluⅠ多态性分析：实验组和对照组均符合H-W遗传平衡定律（P0.05)，实验组Aa、aa基因型频率与对照组相比，差异有统计学意义(P0.05)，而AA基因型和两组等位基因a、A频率的比较，差异无统计学意义(P0.05)。POT1IVS13-98多态性分析：实验组和对照组均符合Hardy-Weinberg(H-W)遗传平衡定律(P0.05)，试验组GG基因型频率与对照组相比，差异显著（P0.05）,试验组等位基因G、T频率与对照组相比亦有差异（P0.05）。而GT、TT分布的比较差异无统计学意义(P0.05)。ERβG1082A基因型与肿瘤的临床分期、分化程度、浸润深度、转移情况、五年生存情况密切相关（P0.05）,与初复发肿瘤、患者年龄、肿瘤大小、组织学类型无关（P0.05）；GenotypeinhPOT1IVS13-98G/T与肿瘤的临床分期、分化程度、浸润深度、转移情况、五年生存情况密切相关（P0.05）,与初复发肿瘤、患者年龄、肿瘤大小、组织学类型无关（P0.05）；而ERβ的CArepeatpolymorphism与胃癌的所有临床特征无关。等位基因频率中仅a/A与肿瘤的分化程度、浸润深度密切相关（P0.01），其余均与肿瘤无关。结论：ERβ和POT1均与胃癌、分化程度、浸润深度、转移及五年存活率密切相关，并且ERβ的Aa、aa基因型及POT1的GG型及等位基因G/T关系极大。[关键词]胃癌，临床特征，ERβ，hPOT1，基因多态性TheExpressionandCorrelationofERβ,hPOT1GeneinGastricCancerandGastricUlcerTissueineasternChina2QianChunye1YangLiucai1,ZhouJuan1,SongSu2(1YanchengHealthVocationalandTechnicalCollege;2YanchengNO.1People'sHospital,224006,China)[Abstract]Objective:ToexplorethepolymorphismsandcorrelationofERβ,hPOT1geneingastriccancerandgastriculcertissue.Methods:100casesofprimarygastriccancerasthetestgroup,90casesgastriculcerasthecontrolgroup,immunohistochemicalSPmethodwasusedtodetectERβandhPOT1protein,RT-PCRmethodtodetectthepolymorphismsofERβCArepeatsequence,G1082AaswellashPOT1genesSNPS.Results:1.PositiveratesofERβwererespectively68.0%and23.3%inthetestgroupandthecontrolgroup,withsignificantdifference(P0.01).WhilethoseofPOT1wererespectively86.0%and1.1%,withsignificantdifference(P0.01);Andthepositiveratesofthesubjectswithlowdifferentiationdegree,highinvasiondepth,lymphnodemetastasisandfiveyearsdeathrespectivelywerehigherthanthosewithhighdifferentiationdegree,shallowinvasiondepth,withoutlymphnodemetastasisandfiveyearssurvival,andtheclinicalstagesⅠ,ⅡwerelowersignificantlythanstageⅢ(P0.01/0.05).AndERβandthepositiveexpressionofERβandPOT1hasnothingtodowithonsetrecurrence,age,tumorsize,andhistologicaltypes(P0.05).Whenthepositiverateofthegeneexpressionincreases,patientshavemorerisktosufferdistantmetastases(P0.001),andfive-yearsurvivalrateisalsodropped(P0.05).2.GenotypedistributionaccordswiththeHardy-Weinberg(H-W)geneticbalanceinERβCArepeatsequence(P0.05);ComparativegenotypeSS,SL,LLdifferencesweren’tstatisticallysignificant(P0.05)，andallelefrequencyS,Lweren’tstatisticallysignificant,either(P0.05).ThispointsoutpolymorphismofCArepeatsequenceexpressionsofERβgenewereunrelatedwithgastriccancer.3.InERβG1082Apolymorphism，analysisofRsaⅠpolymorphism:TwogroupsaccordwiththeH-Wgeneticbalance(P0.05);Comparativegenotyperr,Rr,RRdifferencesweren’tstatisticallysignificant(P0.05);Genotypefrequencyr,Rweren’tstatisticallysignificant,either(P0.05)；analysisofAluⅠpolymorphisminERβ:TwogroupsaccordwiththeH-Wgeneticbalance(P0.05);GenotypeAa,aainthetestgroupwashigherthanthatinthecontrolgroup(P0.05)，butgenotypeAAandallelefrequencyS,Lweren’tstatisticallysignificantP0.05).4.AnalysisofPOT1IVS13-98polymorphism:TwogroupsaccordwiththeH-Wgeneticbalance(P0.05);GenotypeGGinthetestgroupwashigherthanthatinthecontrolgroup(P0.05);GenotypefrequencyG,Twerestatisticallysignificant(P0.05),andallelefrequencyG,Twerestatisticallysignificant,too,butGT,TTdistributionfrequencyweren’tstatisticallysignificant(P0.05).5.GenotypeinG1082ApolymorphismofERβwascloselyrelatedtoclinicalstages,differentiationdegree,infiltrationdepth,metastasessituationandthefive-yearsurvivalcondition（P0.05）,anditwasn’trelatedtoonsetrecurrence,age,tumorsizeandhistologicaltypes（P0.05）；ItwasthesameinGenotypeinhPOT1IVS13-98G/T；ButCArepeatpolymorphismofERβwasn’trelatedtoeveryclinicalfeatureofgastriccancer.Inallelefrequency,onlya/Awascloselyrelatedtodifferentiationdegreeandinfiltrationdepth（P0.01）,buttheothersweren’t.Conclusion:ERβandPOT1polymorphismwascloselyrelatedtoclinicalstages,differentiationdegree,infiltrationdepth,metastasessituationandthefive-yearsurvivalconditioningastriccancer.AndgenotypesAa,aainERβ,GG-typeandallelesG/TinPOT1arerelatedtoeachother.[KeyWords]gastriccancer,clinicalfeatures,ERβ,hPOT1,genepolymorphism胃癌是长江中下游地区高发的消化道肿瘤，其与性激素的关系在前期研究[1,10]中已有报道。而雌激素是其中重要的激素之一，其与雌激素受体（ER）结合而起作用，ER是一种特异蛋白，有两种亚型：ERα和ERβ[1]；人类端粒保护蛋白(humanprotectionoftelomeres1,hPOT1)是端粒单链结合蛋白，可能在细胞分裂、染色体维持、末端保护和端粒长度调控等方面起着广泛的作用，DNA损伤反应导致端粒功能失活，限制了转化细胞