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Poster display session

1940 - A novel CpG panel is independently associated with colorectal cancer survival

Date

09 Sep 2017

Session

Poster display session

Topics

Translational Research;  Colon and Rectal Cancer

Presenters

Min Jia

Citation

Annals of Oncology (2017) 28 (suppl_5): v158-v208. 10.1093/annonc/mdx393

Authors

M. Jia1, Y. Zhang1, L. Jansen1, V. Walter1, D. Edelmann2, M. Maierthaler3, K. Tagscherer4, W. Roth4, M. Bewerunge-Hudler5, E. Herpel6, M. Kloor7, A. Ulrich8, B. Burwinkel3, H. Bläker9, J. Chang-Claude10, H. Brenner1, M. Hoffmeister1

Author affiliations

  • 1 Division Of Clinical Epidemiology And Aging Research, German Cancer Research Center, 69120 - Heidelberg/DE
  • 2 Division Of Biostatistics, German Cancer Research Center, 69120 - Heidelberg/DE
  • 3 Division Of Molecular Epidemiology, German Cancer Research Center, 69120 - Heidelberg/DE
  • 4 Institute Of Pathology, University Medical Center Mainz, 55101 - Mainz/DE
  • 5 Core Facility Genomics & Proteomics, German Cancer Research Center, 69120 - Heidelberg/DE
  • 6 Department Of General Pathology, Institute Of Pathology, University of Heidelberg, 69120 - Heidelberg/DE
  • 7 Department Of Applied Tumor Biology, Institute Of Pathology, Heidelberg University Hospital, 69120 - Heidelberg/DE
  • 8 Department Of General, Visceral And Transplantation Surgery, University of Heidelberg, 69120 - Heidelberg/DE
  • 9 Charité University Medicine, Institute of Pathology, 10117 - Berlin/DE
  • 10 Division Of Cancer Epidemiology, Unit Of Genetic Epidemiology, German Cancer Research Center, 69120 - Heidelberg/DE
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Resources

Abstract 1940

Background

Results of previous studies on the association of the CpG island methylator phenotype (CIMP) with colorectal cancer (CRC) prognosis were inconsistent and the variety of markers selected to define CIMP was widely blamed for the inconsistency. The current study was therefore aimed to comprehensively investigate the associations of DNA methylation at CIMP-related genes with CRC survival.

Methods

Patients with CRC diagnosed between 2003 and 2007 were followed up for a median of 5.2 years and divided into a screening cohort (n = 568) and a validation cohort (n = 308). DNA methylation was measured in tumor tissue using the Illumina Infinium HumanMethylation450 BeadChip. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) of survival after CRC, including adjustment for tumor stage, microsatellite instability, BRAF mutation status and other important factors.

Results

Of 48 genes used to define CIMP in the previous studies, 43 were also covered by the methylation array. In the screening cohort, ten CpG sites were identified to be associated with CRC survival. Seven of these ten CpG sites were also associated with CRC survival in the validation cohort and were used to construct a prognostic score. CRC patients with a prognostic score in the lowest tertile (lowest methylation levels at the CpG sites) showed poorer disease-specific survival compared with patients in the highest tertile in both the study cohort and the validation cohort (HR = 3.11; 95% CI = 1.97-4.91 and HR = 3.06; 95% CI = 1.71-5.45 respectively).

Conclusions

A CpG panel consisting of seven CpG sites was found to be strongly associated with CRC survival, independent from important clinical factors and mutations associated with CIMP.

Clinical trial identification

Legal entity responsible for the study

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center

Funding

The German Research Council, the German Federal Ministry of Education and Research

Disclosure

All authors have declared no conflicts of interest.

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