Polymorphism rs4919510CG in Mature Sequence of Human MicroRNA-608 Contributes to the Risk of HER2-Positive Breast Cancer but Not Other Subtypes 英文参考文献.docVIP
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Polymorphism rs4919510CG in Mature Sequence of Human MicroRNA-608 Contributes to the Risk of HER2-Positive Breast Cancer but Not Other Subtypes 英文参考文献
Polymorphismrs4919510:C.GinMatureSequenceof
HumanMicroRNA-608ContributestotheRiskofHER2-
PositiveBreastCancerbutNotOtherSubtypes
A-JiHuang.,Ke-DaYu.,JingLi.,LeiFan,Zhi-MingShao*
DepartmentofBreastSurgery,CancerCenterandCancerInstitute,ShanghaiMedicalCollege,FudanUniversity,Shanghai,People’sRepublicofChina
Abstract
Background: A few polymorphisms are located in the mature microRNA sequences. Such polymorphisms could directly
affectthebindingofmicroRNAtohundredsoftargetmRNAs.Itremainsunknownwhetherrs4919510:C.Glocatedinthe
maturemiR-608altersbreastcancersusceptibility.
Methods:Theassociationofrs4919510:C.Gwithriskandpathologicfeaturesofbreastcancerwereinvestigatedintwo
independentcase-controlstudies,thefirstsetincluding1,138sporadicbreastcancerpatients(including927invasiveductal
carcinomapatients,777ofthemwithknownsubtypes:496luminal-like,133HER2-positive,and148triple-negative)and
1,434 community-based controls, and the second set including 294 familial/early-onset breast cancer patients and 500
hospital-basedcancer-freecontrols.Oddsratios(ORs)wereestimatedbylogisticregression.PredictedtargetsofmiR-608
andcomplementarysequencescontainingrs4919510:C.Gweresurveyedtorevealpotentialpathologicalmechanism.
Results:Inthefirstset,althoughrs4919510:C.Gwasunrelatedtobreastcanceringeneralpatients,variantgenotypes(CG/
GG)werespecificallyassociatedwithincreasedriskofHER2-positivesubtype(AdjustedOR=1.97,95%CI,1.3422.90inthe
recessivemodel).VariantG-allelewastheriskallelewithORof1.62(95%CI,1.2322.15).PatientscarryingGG-genotypealso
had larger HER2-positive tumors (P for Kruskal-Wallis test=0.006). The relationship between rs4919510:C.G and risk of
HER2-positivesubgroupwasvalidatedinthesecondset(BonferronicorrectedP=0.06).TheadjustedcombinedOR(total
164HER2-positivecases)intherecessivemodelwas1.97(95%CI,1.4322.72)forGGgenotype(correctedP=1.161024
).
Bioinformaticanalysisindicatedthat,HSF1,whichisrequiredforHER2-inducedtumorigenesis,mightbeatargetofmiR-608.
Theminimumfree-energyofan
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