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000127475 1001_ $$0P:(DE-He78)c67a12496b8aac150c0eef888d808d46$$aSchöttker, Ben$$b0$$eFirst author$$udkfz
000127475 245__ $$aDiscovery of a novel epigenetic cancer marker related to the oxidative status of human blood.
000127475 260__ $$aNew York, NY$$bWiley-Liss$$c2015
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000127475 520__ $$aLong-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.
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000127475 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor
000127475 650_7 $$2NLM Chemicals$$aReactive Oxygen Species
000127475 7001_ $$0P:(DE-He78)6a8f87626cb610618a60d742677284cd$$aZhang, Yan$$b1$$udkfz
000127475 7001_ $$0P:(DE-He78)d3e4e449f4ed4d38e6ec44362e89dbc8$$aHeiss, Jonathan$$b2$$udkfz
000127475 7001_ $$0P:(DE-He78)7ca7eafba864e5c3ebb7598149380452$$aButterbach, Katja$$b3$$udkfz
000127475 7001_ $$aJansen, Eugène H J M$$b4
000127475 7001_ $$0P:(DE-He78)7999346780553d7fab7ba69d5afdfa71$$aBewerunge-Hudler, Melanie$$b5$$udkfz
000127475 7001_ $$0P:(DE-He78)97343bbd9545a4b87574e74329dabfd1$$aSaum, Kai-Uwe$$b6$$udkfz
000127475 7001_ $$aHolleczek, Bernd$$b7
000127475 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b8$$eLast author$$udkfz
000127475 773__ $$0PERI:(DE-600)1492641-6$$a10.1002/gcc.22271$$gVol. 54, no. 9, p. 583 - 594$$n9$$p583 - 594$$tGenes, chromosomes & cancer$$v54$$x1045-2257$$y2015
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