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dc.contributor.authorMayers, Jared R.
dc.contributor.authorTorrence, Margaret E.
dc.contributor.authorFiske, Brian Prescott
dc.contributor.authorDavidson, Shawn Michael
dc.contributor.authorPapagiannakopoulos, Thales
dc.contributor.authorDayton, Talya Lucia
dc.contributor.authorVander Heiden, Matthew G.
dc.date.accessioned2015-04-28T19:11:55Z
dc.date.available2015-04-28T19:11:55Z
dc.date.issued2014-09
dc.date.submitted2014-06
dc.identifier.issn1078-8956
dc.identifier.issn1546-170X
dc.identifier.urihttp://hdl.handle.net/1721.1/96828
dc.description.abstractMost patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months. PDAC has been linked with obesity and glucose intolerance, but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from individuals with pancreatic cancer (cases) and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years before diagnosis, when occult disease is probably present. We show that plasma BCAAs are also elevated in mice with early-stage pancreatic cancers driven by mutant Kras expression but not in mice with Kras-driven tumors in other tissues, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early-stage disease. Together, these findings suggest that increased whole-body protein breakdown is an early event in development of PDAC.en_US
dc.description.sponsorshipGrant F30 CA183474en_US
dc.description.sponsorshipBurroughs Wellcome Funden_US
dc.description.sponsorshipDamon Runyon Cancer Research Foundationen_US
dc.description.sponsorshipSmith Family Foundationen_US
dc.description.sponsorshipStern Familyen_US
dc.description.sponsorshipP30-CA14051en_US
dc.description.sponsorshipP01-CA117969en_US
dc.description.sponsorshipLustgarten Foundationen_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/nm.3686en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titleElevated circulating branched chain amino acids are an early event in pancreatic adenocarcinoma developmenten_US
dc.title.alternativeElevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma developmenten_US
dc.typeArticleen_US
dc.identifier.citationMayers, Jared R, Chen Wu, Clary B Clish, Peter Kraft, Margaret E Torrence, Brian P Fiske, Chen Yuan, et al. “Elevation of Circulating Branched-Chain Amino Acids Is an Early Event in Human Pancreatic Adenocarcinoma Development.” Nature Medicine 20, no. 10 (September 28, 2014): 1193–1198.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorMayers, Jared R.en_US
dc.contributor.mitauthorTorrence, Margaret E.en_US
dc.contributor.mitauthorFiske, Brian Prescotten_US
dc.contributor.mitauthorDavidson, Shawn Michaelen_US
dc.contributor.mitauthorPapagiannakopoulos, Thalesen_US
dc.contributor.mitauthorDayton, Talya Luciaen_US
dc.contributor.mitauthorVander Heiden, Matthew G.en_US
dc.relation.journalNature Medicineen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsMayers, Jared R; Wu, Chen; Clish, Clary B; Kraft, Peter; Torrence, Margaret E; Fiske, Brian P; Yuan, Chen; Bao, Ying; Townsend, Mary K; Tworoger, Shelley S; Davidson, Shawn M; Papagiannakopoulos, Thales; Yang, Annan; Dayton, Talya L; Ogino, Shuji; Stampfer, Meir J; Giovannucci, Edward L; Qian, Zhi Rong; Rubinson, Douglas A; Ma, Jing; Sesso, Howard D; Gaziano, John M; Cochrane, Barbara B; Liu, Simin; Wactawski-Wende, Jean; Manson, JoAnn E; Pollak, Michael N; Kimmelman, Alec C; Souza, Amanda; Pierce, Kerry; Wang, Thomas J; Gerszten, Robert E; Fuchs, Charles S; Vander Heiden, Matthew G; Wolpin, Brian Men_US
dc.identifier.orcidhttps://orcid.org/0000-0002-8607-1787
dc.identifier.orcidhttps://orcid.org/0000-0002-6702-4192
dc.identifier.orcidhttps://orcid.org/0000-0001-9587-0233
dc.identifier.orcidhttps://orcid.org/0000-0003-0701-5275
dc.identifier.orcidhttps://orcid.org/0000-0002-7994-7963
mit.licensePUBLISHER_POLICYen_US


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