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dc.contributor.authorOgino, Shuji
dc.contributor.authorNosho, Katsuhiko
dc.contributor.authorKirkner, Gregory J.
dc.contributor.authorKawasaki, Takako
dc.contributor.authorChan, Andrew T.
dc.contributor.authorSchernhammer, Eva S.
dc.contributor.authorGiovannucci, Edward L.
dc.contributor.authorFuchs, Charles S.
dc.date.accessioned2019-09-23T15:33:31Z
dc.date.issued2008
dc.identifier.citationOgino, Shuji, Katsuhiko Nosho, Gregory J. Kirkner, Takako Kawasaki, Andrew T. Chan, Eva S. Schernhammer, Edward L. Giovannucci, and Charles S. Fuchs. 2008. “A Cohort Study of Tumoral LINE-1 Hypomethylation and Prognosis in Colon Cancer.” JNCI: Journal of the National Cancer Institute 100 (23): 1734–38. https://doi.org/10.1093/jnci/djn359.
dc.identifier.issn0027-8874
dc.identifier.issn0198-0157
dc.identifier.issn1460-2105
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41391984*
dc.description.abstractGenome-wide DNA hypomethylation plays has an important role in genomic instability and colorectal carcinogenesis. However, the relationship between cellular DNA methylation level and patient outcome remains uncertain. Using 643 colon cancers in two independent prospective cohorts, we quantified DNA methylation in repetitive long interspersed nucleotide element-1 (LINE-1) elements using pyrosequencing, which is a good indicator of global DNA methylation level. We used Cox proportional hazard models to calculate hazard ratios (HRs) of colon cancer-specific and overall mortality, adjusting for patient and tumoral features, including CpG island methylator phenotype (CIMP). Statistical tests were two-sided. LINE-1 hypomethylation was linearly associated with a statistically significant increase in colon cancer-specific mortality (for a 30% decrease in LINE-1 methylation: multivariable HR = 2.37, 95% confidence interval [CI] = 1.42 to 3.94; P(trend) < .001) and overall mortality (multivariable HR = 1.85, 95% CI = 1.25 to 2.75; P(trend) = .002). The association was consistent across the two independent cohorts and strata of clinical and molecular characteristics, including sex, age, tumor location, stage, and CIMP, microsatellite instability, KRAS, BRAF, p53, and chromosomal instability status. In conclusion, tumoral LINE-1 hypomethylation is independently associated with shorter survival among colon cancer patients.
dc.language.isoen_US
dc.publisherOxford University Press
dash.licenseMETA_ONLY
dc.titleA Cohort Study of Tumoral LINE-1 Hypomethylation and Prognosis in Colon Cancer
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalJournal of the National Cancer Institute
dash.depositing.authorGiovannucci, Edward L.::fd8dcb59a5a5859f2a85fabae12a60cf::600
dc.date.available2019-09-23T15:33:31Z
dash.workflow.comments1Science Serial ID 61947
dc.identifier.doi10.1093/jnci/djn359
dash.source.volume100;23
dash.source.page1734


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