Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival

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Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival

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Title: Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival
Author: Mima, Kosuke; Nowak, Jonathan A.; Qian, Zhi Rong; Cao, Yin; Song, Mingyang ORCID  0000-0002-1324-0316 ; Masugi, Yohei; Shi, Yan; da Silva, Annacarolina; Gu, Mancang; Li, Wanwan; Hamada, Tsuyoshi; Zhang, Xuehong; Wu, Kana; Meyerhardt, Jeffrey A.; Baba, Hideo; Giovannucci, Edward L.; Chan, Andrew T.; Fuchs, Charles S.; Ogino, Shuji; Nishihara, Reiko

Note: Order does not necessarily reflect citation order of authors.

Citation: Mima, K., J. A. Nowak, Z. R. Qian, Y. Cao, M. Song, Y. Masugi, Y. Shi, et al. 2016. “Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival.” Oncotarget 7 (34): 55098-55109. doi:10.18632/oncotarget.10398. http://dx.doi.org/10.18632/oncotarget.10398.
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Abstract: Colorectal tumors arise with genomic and epigenomic alterations through interactions between neoplastic cells, immune cells, and microbiota that vary along the proximal to distal axis of colorectum. Long interspersed nucleotide element-1 (LINE-1) hypomethylation in colorectal cancer has been associated with worse clinical outcome. Utilizing 1,317 colon and rectal carcinoma cases in two U.S.-nationwide prospective cohort studies, we examined patient survival according to LINE-1 methylation level stratified by tumor location. Cox proportional hazards model was used to assess a statistical interaction between LINE-1 methylation level and tumor location in colorectal cancer-specific mortality analysis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, and KRAS, BRAF, and PIK3CA mutations. A statistically significant interaction was found between LINE-1 methylation level and tumor location in colorectal cancer-specific mortality analysis (Pinteraction = 0.011). The association of LINE-1 hypomethylation with higher colorectal cancer-specific mortality was stronger in proximal colon cancers (multivariable hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.21 to 2.28) than in distal colon cancers (multivariable HR, 1.18; 95% CI, 0.81 to 1.72) or rectal cancers (multivariable HR, 0.87; 95% CI, 0.57 to 1.34). Our data suggest the interactive effect of LINE-1 methylation level and colorectal cancer location on clinical outcome.
Published Version: doi:10.18632/oncotarget.10398
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342404/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32072212
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