Genome-wide DNA methylation differences according to oestrogen receptor beta status in colorectal cancer

Involvement of sex hormones in colorectal cancer (CRC) development has been linked to oestrogen receptor β (ERβ). Expression of ERβ is found reduced in tumour tissue and inversely related to mortality. However, mechanisms are not well understood. Our study aimed to detect differentially methylated g...

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Bibliographic Details
Published in:Epigenetics 2019-05, Vol.14 (5), p.477-493
Main Authors: Neumeyer, Sonja, Popanda, Odilia, Edelmann, Dominic, Butterbach, Katja, Toth, Csaba, Roth, Wilfried, Bläker, Hendrik, Jiang, Ruijingfang, Herpel, Esther, Jäkel, Cornelia, Schmezer, Peter, Jansen, Lina, Alwers, Elizabeth, Benner, Axel, Burwinkel, Barbara, Hoffmeister, Michael, Brenner, Hermann, Chang-Claude, Jenny
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor - genetics
Case-Control Studies
Colon
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
differential methylation
DNA Methylation
Epigenesis, Genetic
epigenetics
ERβ
Estrogen Receptor beta - metabolism
EWAS
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Genome-Wide Association Study
Humans
Male
methylation profiling
Middle Aged
Prognosis
Promoter Regions, Genetic
Research Paper
sex hormones
Survival Rate
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Summary:Involvement of sex hormones in colorectal cancer (CRC) development has been linked to oestrogen receptor β (ERβ). Expression of ERβ is found reduced in tumour tissue and inversely related to mortality. However, mechanisms are not well understood. Our study aimed to detect differentially methylated genes associated with ERβ expression, which could point to mechanisms by which ERβ could influence risk and prognosis of CRC. Epigenome-wide DNA methylation profiling was performed using Illumina HumanMethylation450k BeadChip arrays in two independent tumour sample sets of CRC patients recruited in 2003-2010 by the German DACHS study (discovery cohort n = 917, replication cohort n = 907). ERβ expression was measured using immunohistochemistry and scored as negative, moderate and high. Differentially methylated CpG sites and genomic regions were determined using limma in the R-package RnBeads. For the comparison of tumours with moderate/high ERβ versus negative expression, differentially methylated CpG sites were identified but not confirmed by replication. Comparing tumours of high with tumours of negative ERβ expression revealed 2,904 differentially methylated CpG sites of which 403 were replicated (FDR adjusted p-value
ISSN:1559-2294
1559-2308
DOI:10.1080/15592294.2019.1595998