Show simple item record

dc.contributor.authorNosho, Katsuhiko
dc.contributor.authorKure, Shoko
dc.contributor.authorIrahara, Natsumi
dc.contributor.authorShima, Kaori
dc.contributor.authorBaba, Yoshifumi
dc.contributor.authorSpiegelman, Donna
dc.contributor.authorMeyerhardt, Jeffrey A.
dc.contributor.authorGiovannucci, Edward L.
dc.contributor.authorFuchs, Charles S.
dc.contributor.authorOgino, Shuji
dc.date.accessioned2019-09-21T16:10:13Z
dc.date.issued2009
dc.identifier.citationNosho, Katsuhiko, Shoko Kure, Natsumi Irahara, Kaori Shima, Yoshifumi Baba, Donna Spiegelman, Jeffrey A. Meyerhardt, Edward L. Giovannucci, Charles S. Fuchs, and Shuji Ogino. 2009. “A Prospective Cohort Study Shows Unique Epigenetic, Genetic, and Prognostic Features of Synchronous Colorectal Cancers.” Gastroenterology 137 (5): 1609–1620.e3. https://doi.org/10.1053/j.gastro.2009.08.002.
dc.identifier.issn0016-5085
dc.identifier.issn1528-0012
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41384608*
dc.description.abstractBACKGROUND and AIMS: Synchronous colorectal neoplasias (2 or more primary carcinomas identified in the same patient) are caused by common generic and environmental factors and can be used to study the field effect. Synchronous colon cancers have not been compared with control solitary cancers in a prospective study. METHODS: We analyzed data collected from 47 patients with synchronous colorectal cancers and 2021 solitary colorectal cancers (controls) in 2 prospective cohort studies. Tumors samples were analyzed for methylation in LINE-1 and 16 CpG islands (CACNA1G, CDKN2A [p16], CRABP1, IGF2, MLH1, NEUROG1, RUNX3, SOCS1, CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14 [ARF], and WRN); microsatellite instability (MSI); the CpG island methylator phenotype (CIMP); 18q loss of heterozygosity; KRAS, BRAF, and PIK3CA mutations; and expression of beta-catenin, p53, p21, p27, cyclin D1, fatty acid synthase, and cyclooxygenase-2. RESULTS: Compared with patients with solitary colorectal cancer, synchronous colorectal cancer patients had reduced overall survival time (log-rank, P = .0048; hazard ratio [HR], 1.71; 95% confidence interval [CI]: 1.17-2.50; P = .0053; multivariate HR, 1.47; 9S% CI: 1.00-2.17; P = .049). Compared with solitary rumors, synchronous tumors more frequently contained BRAF mutations (P = .0041), CIMP-high (P = .013), and MSI-high (P = .037). Methylation levels of LINE-1 (Spearman r = 0.82; P = .0072) and CpG island methylation (P < .0001) correlated between synchronous cancer pairs from the same individuals. CONCLUSIONS: Synchronous colorectal cancers had more frequent mutations in BRAF, were more frequently CIMP- and MSI-high, and had a worse prognosis than solitary colorectal cancers. Similar epigenomic and epigenetic events were frequently observed within a synchronous cancer pair, suggesting the presence of a field defect.
dc.language.isoen_US
dc.publisherElsevier
dash.licenseLAA
dc.titleA Prospective Cohort Study Shows Unique Epigenetic, Genetic, and Prognostic Features of Synchronous Colorectal Cancers
dc.typeJournal Article
dc.description.versionAccepted Manuscript
dc.relation.journalGastroenterology
dash.depositing.authorSpiegelman, Donna::37eeac21962b33e4e46e7aedde542849::600
dc.date.available2019-09-21T16:10:13Z
dash.workflow.comments1Science Serial ID 34531
dc.identifier.doi10.1053/j.gastro.2009.08.002
dash.source.volume137;5
dash.source.page1609


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record