Association of Caucasian-Identified Variants with Colorectal Cancer Risk in Singapore Chinese 英文参考文献.docVIP

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Association of Caucasian-Identified Variants with Colorectal Cancer Risk in Singapore Chinese 英文参考文献.doc

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Association of Caucasian-Identified Variants with Colorectal Cancer Risk in Singapore Chinese 英文参考文献

AssociationofCaucasian-IdentifiedVariantswith ColorectalCancerRiskinSingaporeChinese LaiFunThean1,HuiHuaLi2,YikYingTeo3,Woon-PuayKoh3,Jian-MinYuan4,MeiLinTeoh5 ,Poh KoonKoh1,ChoongLeongTang1,PehYeanCheah1,3,6* 1DepartmentofColorectalSurgery,SingaporeGeneralHospital,Singapore,2DepartmentofClinicalResearch,SingaporeGeneralHospital,Singapore,Singapore,3Saw SweeHockSchoolofPublicHealth,NationalUniversityofSingapore,Singapore,4UniversityofPittsburghCancerInstitute,andDepartmentofEpidemiology,Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 5Health Screening Unit, Singapore General Hospital, Singapore Singapore,6Duke-NationalUniversityofSingapore,GraduateMedicalSchool,NationalUniversityofSingapore,Singapore Abstract Background: Genome-wide association studies (GWAS) in Caucasians have identified fourteen index single nucleotide polymorphisms(iSNPs)thatinfluencecolorectalcancer(CRC)risk. Methods:WeinvestigatedtheroleofeleveniSNPsorsurrogateSNPs(sSNPs),inhighlinkagedisequilibrium(LD,r2$0.8) andwithin100kbvicinityofiSNPs,in2,000age-andgender-matchedSingaporeChinese(SCH)casesandcontrols. Results:OnlyiSNPrs6983267at8q24.21andsSNPsrs6695584,rrs3087967,rs2059254,andrs7226855at1q41, 8q23.3, 11q23.1, 16q22.1 and 18q21.1 respectively showed evidence of association with CRC risk, with odds ratios (OR) rangingfrom1.13to1.40.sSNPrs827401at10p14wasassociatedwithrectalcancerrisk(OR=0.74,95%CI0.63–0.88)but notdiseaseprognosis(OR=0.91,95%CI0.69–1.20).Interestingly,sSNPrs3087967at11q23.1wasassociatedwithCRCriskin men(OR=1.34,95%CI1.14–1.58)butnotwomen(OR=1.07,95%CI:0.88–1.29),suggestingagender-specificrole.Halfof theCaucasian-identifiedvariants,includingtherecentlyfine-mappedBMPpathwayloci,BMP4,GREM1,BMP2andLAMA5, didnotshowanyevidenceforassociationwithCRCinSCH(OR,1;p-value.0.1).Comparingtheresultsofthisstudywith thatoftheNorthernandHongKongChinese,onlyvariantsatchromosomes8q24.21,10p14,11q23.1and18q21.1were replica