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

Kosuke Mima, Jonathan A. Nowak, Zhi Rong Qian, Yin Cao, Mingyang Song, Yohei Masugi, Yan Shi, Annacarolina da Silva, Mancang Gu, Wanwan Li, Tsuyoshi Hamada, Xuehong Zhang, Kana Wu, Jeffrey A. Meyerhardt, Hideo Baba, Edward L. Giovannucci, Andrew T. Chan, Charles S. Fuchs, Shuji Ogino, Reiko Nishihara

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)55098-55109
Number of pages12
JournalOncotarget
Volume7
Issue number34
DOIs
Publication statusPublished - 2016

Keywords

  • Epigenetics
  • Left-sided
  • Molecular pathological epidemiology
  • Prognosis
  • Right-sided

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Mima, K., Nowak, J. A., Qian, Z. R., Cao, Y., Song, M., Masugi, Y., Shi, Y., da Silva, A., Gu, M., Li, W., Hamada, T., Zhang, X., Wu, K., Meyerhardt, J. A., Baba, H., Giovannucci, E. L., Chan, A. T., Fuchs, C. S., Ogino, S., & Nishihara, R. (2016). Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival. Oncotarget, 7(34), 55098-55109. https://doi.org/10.18632/oncotarget.10398