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dc.contributor.authorPeters, Ulrike
dc.contributor.authorJiao, Shuo
dc.contributor.authorSchumacher, Fredrick R.
dc.contributor.authorHutter, Carolyn M.
dc.contributor.authorAragaki, Aaron K.
dc.contributor.authorBaron, John A.
dc.contributor.authorBerndt, Sonja I.
dc.contributor.authorBézieau, Stéphane
dc.contributor.authorBrenner, Hermann
dc.contributor.authorButterbach, Katja
dc.contributor.authorCaan, Bette J.
dc.contributor.authorCampbell, Peter T.
dc.contributor.authorCarlson, Christopher S.
dc.contributor.authorCasey, Graham
dc.contributor.authorChan, Andrew T.
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorChanock, Stephen J.
dc.contributor.authorChen, Lin S.
dc.contributor.authorCoetzee, Gerhard A.
dc.contributor.authorCoetzee, Simon G.
dc.contributor.authorConti, David V.
dc.contributor.authorCurtis, Keith R.
dc.contributor.authorDuggan, David
dc.contributor.authorEdwards, Todd
dc.contributor.authorFuchs, Charles S.
dc.contributor.authorGallinger, Steven
dc.contributor.authorGiovannucci, Edward L.
dc.contributor.authorGogarten, Stephanie M.
dc.contributor.authorGruber, Stephen B.
dc.contributor.authorHaile, Robert W.
dc.contributor.authorHarrison, Tabitha A.
dc.contributor.authorHayes, Richard B.
dc.contributor.authorHenderson, Brian E.
dc.contributor.authorHoffmeister, Michael
dc.contributor.authorHopper, John L.
dc.contributor.authorHudson, Thomas J.
dc.contributor.authorHunter, David J.
dc.contributor.authorJackson, Rebecca D.
dc.contributor.authorJee, Sun Ha
dc.contributor.authorJenkins, Mark A.
dc.contributor.authorJia, Wei-Hua
dc.contributor.authorKolonel, Laurence N.
dc.contributor.authorKooperberg, Charles
dc.contributor.authorKüry, Sébastien
dc.contributor.authorLacroix, Andrea Z.
dc.contributor.authorLaurie, Cathy C.
dc.contributor.authorLaurie, Cecelia A.
dc.contributor.authorMarchand, Loic Le
dc.contributor.authorLemire, Mathieu
dc.contributor.authorLevine, David
dc.contributor.authorLindor, Noralane M.
dc.contributor.authorLiu, Yan
dc.contributor.authorMa, Jing
dc.contributor.authorMakar, Karen W.
dc.contributor.authorMatsuo, Keitaro
dc.contributor.authorNewcomb, Polly A.
dc.contributor.authorPotter, John D.
dc.contributor.authorPrentice, Ross L.
dc.contributor.authorQu, Conghui
dc.contributor.authorRohan, Thomas
dc.contributor.authorRosse, Stephanie A.
dc.contributor.authorSchoen, Robert E.
dc.contributor.authorSeminara, Daniela
dc.contributor.authorShrubsole, Martha
dc.contributor.authorShu, Xiao-Ou
dc.contributor.authorSlattery, Martha L.
dc.contributor.authorTaverna, Darin
dc.contributor.authorThibodeau, Stephen N.
dc.contributor.authorUlrich, Cornelia M.
dc.contributor.authorWhite, Emily
dc.contributor.authorXiang, Yongbing
dc.contributor.authorZanke, Brent W.
dc.contributor.authorZeng, Yi-Xin
dc.contributor.authorZhang, Ben
dc.contributor.authorZheng, Wei
dc.contributor.authorHsu, Li
dc.date.accessioned2019-09-23T15:33:58Z
dc.date.issued2013
dc.identifier.citationPeters, Ulrike, Shuo Jiao, Fredrick R. Schumacher, Carolyn M. Hutter, Aaron K. Aragaki, John A. Baron, Sonja I. Berndt, et al. 2013. “Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-Analysis.” Gastroenterology 144 (4): 799–807.e24. https://doi.org/10.1053/j.gastro.2012.12.020.
dc.identifier.issn0016-5085
dc.identifier.issn1528-0012
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41392037*
dc.description.abstractBACKGROUND and AIMS: Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis. METHODS: We conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent. RESULTS: Based on the combined analysis, we identified a locus that reached the conventional genome-wide significance level at less than 5.0 X 10(-8): an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 X 10(-8)). We also found evidence for 3 additional loci with P values less than 5.0 X 10(-7): a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 X 10(-8)), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 X 10(-8)), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 X 10(-7)). CONCLUSIONS: In a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to beta-catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation.
dc.language.isoen_US
dc.publisherElsevier
dash.licenseOAP
dc.titleIdentification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-wide Meta-analysis
dc.typeJournal Article
dc.description.versionAccepted Manuscript
dc.relation.journalGastroenterology
dash.depositing.authorGiovannucci, Edward L.::fd8dcb59a5a5859f2a85fabae12a60cf::600
dc.date.available2019-09-23T15:33:58Z
dash.workflow.comments1Science Serial ID 34552
dc.identifier.doi10.1053/j.gastro.2012.12.020
dash.source.volume144;4
dash.source.page799


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