Journal Article

DKFZ-2017-03498

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Discovery of a novel epigenetic cancer marker related to the oxidative status of human blood.

Schöttker, B. (First author)DKFZ* ; Zhang, Y.DKFZ* ; Heiss, J.DKFZ* ; Butterbach, K.DKFZ* ; Jansen, E. H. J. M. ; Bewerunge-Hudler, M.DKFZ* ; Saum, K.-U.DKFZ* ; Holleczek, B. ; Brenner, H. (Last author)DKFZ*

2015
Wiley-Liss New York, NY

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Please use a persistent id in citations: doi:10.1002/gcc.22271

Abstract: Long-lasting oxidative stress exposure may lead to relatively stable epigenetic modifications of the DNA in order to activate anti-oxidative defence mechanisms. Oxidative stress related DNA methylation may therefore be associated (causally or as a by-product) with cancer. We measured derivatives of reactive oxygen metabolites (D-ROM), total thiol levels (TTL) and DNA methylation with the Illumina Infinium 450K BeadChip in three samples of German individuals aged ≥50 years: n = 1,000 ESTHER study baseline participants (DNA methylation only), n = 99 ESTHER eight-year follow-up participants and n = 142 participants of the BLITZ study. The correlation coefficient of methylation at cg10342304 and D-ROM in the ESTHER 8-year follow-up sample (r = -0.427; P = 1 × 10(-5)) was replicated with a P-value indicating statistical significance after correction for multiple testing in the BLITZ sample (r = -0.192; P = 0.022). The association was robust to adjusting for potential confounders. In the ESTHER baseline sample, the hazard ratio for cancer development in 11 years of follow-up comparing bottom and top quartile of DNA methylation at cg10342304 was 1.86 (95%-confidence-interval 1.01-3.43). In summary, this first epigenome-wide screening and replication study with oxidative status markers observed a negative correlation of D-ROM levels and DNA methylation at cg10342304 in two independent cohorts. This CpG site is located in the body region of the nucleoredoxin gene. The nucleoredoxin protein is a redox-dependent inhibitor of the Wnt/ß-catenin signaling pathway, a well-characterized cancer pathway. If the observed CpG-cancer association can be successfully replicated by other studies, this epigenetic marker could be an interesting biomarker of cancer risk.

Keyword(s): Biomarkers, Tumor ; Reactive Oxygen Species

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Contributing Institute(s):

1. Klinische Epidemiologie und Alternsforschung (C070)
2. Microarray Unit (W110)
3. Präventive Onkologie (G110)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2015

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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