Parallel Routes of Human Carcinoma Development Implications of the Age-Specific Incidence Data 英文参考文献.docVIP

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Parallel Routes of Human Carcinoma Development Implications of the Age-Specific Incidence Data 英文参考文献.doc

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Parallel Routes of Human Carcinoma Development Implications of the Age-Specific Incidence Data 英文参考文献

ParallelRoutesofHumanCarcinomaDevelopment: ImplicationsoftheAge-SpecificIncidenceData JamesP.Brody* DepartmentofBiomedicalEngineeringUniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica Abstract Background: The multi-stage hypothesis suggests that cancers develop through a single defined series of genetic alterations.Thishypothesiswasfirstsuggestedover50yearsagobaseduponage-specificincidencedata.However,recent molecularstudiesoftumorsindicatethatmultipleroutesexisttotheformationofcancer,notasingleroute.Thisparallel routehypothesishasnotbeentestedwithage-specificincidencedata. Methodology/PrincipalFindings:Totesttheparallelroutehypothesis,Iformulateditintermsofamathematicalequation and then tested whether this equation was consistent with age-specific incidence data compiled by the Surveillance EpidemiologyandEndResults(SEER)cancerregistriessince1973.Iusedthechi-squaredgoodnessoffittesttomeasure consistency.Theage-specificincidencedatafrommosthumancarcinomas,includingthoseofthecolon,lung,prostate,and breastwereconsistentwiththeparallelroutehypothesis.However,thishypothesisisonlyconsistentifanimmunesub- population exists, one that will never develop carcinoma. Furthermore, breast carcinoma has two distinct forms of the disease,andoneoftheseoccursatsignificantlydifferentratesindifferentracialgroups. Conclusions/Significance:Iconcludethattheparallelroutehypothesisisconsistentwiththeage-specificincidencedata onlyifcarcinomaoccursinadistinctsubpopulation,whilethemulti-stagehypothesisisinconsistentwiththisdata. Citation:BrodyJP(2009)ParallelRoutesofHumanCarcinomaDevelopment:ImplicationsoftheAge-SpecificIncidenceData.PLoSONE4(9):e7053.doi:10.1371/ journal.pone.0007053 Editor:FabioRapallo,UniversityofEastPiedmont,Italy ReceivedJune11,2009;AcceptedAugust24,2009;PublishedSeptember23,2009 Copyright: ? 2009 Brody et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribut