Potential Excess Mortality in BRCA12 Mutation Carriers beyond Breast, Ovarian, Prostate, and Pancreatic Cancers, and Melanoma 英文参考文献.docVIP

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Potential Excess Mortality in BRCA12 Mutation Carriers beyond Breast, Ovarian, Prostate, and Pancreatic Cancers, and Melanoma 英文参考文献.doc

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Potential Excess Mortality in BRCA12 Mutation Carriers beyond Breast, Ovarian, Prostate, and Pancreatic Cancers, and Melanoma 英文参考文献

PotentialExcessMortalityinBRCA1/2MutationCarriers beyondBreast,Ovarian,Prostate,andPancreatic Cancers,andMelanoma PhuongL.Mai1.*,NilanjanChatterjee2.,PatriciaHartge3,MargaretTucker4,LawrenceBrody5,JefferyP. Struewing5,SholomWacholder2 1ClinicalGeneticBranch,NationalCancerInstitute,Rockville,Maryland,UnitedStatesofAmerica, 2BiostatisticsBranch,NationalCancerInstitute,Rockville,Maryland, United States ofAmerica, 3Office ofDirector of the Biostatistics and EpidemiologyProgram, National Cancer Institute, Rockville, Maryland, United States of America, 4GeneticEpidemiologyBranchoftheDivisionofCancerEpidemiologyandGenetics,NationalCancerInstitute,Rockville,Maryland,UnitedStatesofAmerica,5National HumanGenomeResearchInstitute,Rockville,Maryland,UnitedStatesofAmerica Abstract Background:Althoughtheincreaseinriskofdevelopingbreast,ovarian,andprostatecancerinBRCA1andBRCA2mutation carriers has been studied extensively, its impact on mortality is not well quantified. Further, possible effect of BRCA mutationsonnon-cancermortalityriskhasnotbeenexamined. Methodology/Principal Findings: Usingmortality datafrom therelativesof5,287 genotyped participants, of whom120 carriedaBRCAAshkenaziJewishfoundermutation,inacommunity-basedstudyoftheAshkenaziJewishpopulationinthe WashingtonD.Carea,weexaminedtheassociationbetweenthethreeAshkenaziBRCAfoundermutationsandriskofoverall and non-cancer mortality. To examine risks beyond the established effects of these mutations, we analyzed the data excludingbothdeathsandfollow-uptimesafterreporteddiagnosisofmelanomaandcancerofthebreast,ovary,prostate, andpancreas.Usinganextensionofthekin-cohortmethodthataccountsforinformativecensoring,weestimatedthat,in theabsenceofbreast,ovarian,andpancreaticcancers,andmelanoma,femalecarriershadalifeexpectancythatwas6.8 yearslower(95%CI:1.2–10.5)thannon-carriers.Inmalemutationcarriers,thereductioninlifeexpectancy,intheabsenceof prostateandpancreaticcancersandmelanoma,was3.7(95%CI:20.4,6.8)years.Whendeathsand