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000130650 1001_ $$0P:(DE-He78)a4faf5b3a2d51ffde33f91590be3d539$$aTang, Qiuqiong$$b0$$eFirst author$$udkfz
000130650 245__ $$aDNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1 and RAPSN hypomethylation in peripheral blood DNA.
000130650 260__ $$a[S.l.]$$bImpact Journals LLC$$c2016
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000130650 520__ $$aDNA methylation changes in peripheral blood DNA have been shown to be associated with solid tumors. We sought to identify methylation alterations in whole blood DNA that are associated with breast cancer (BC). Epigenome-wide DNA methylation profiling on blood DNA from BC cases and healthy controls was performed by applying Infinium HumanMethylation450K BeadChips. Promising CpG sites were selected and validated in three independent larger sample cohorts via MassARRAY EpiTyper assays. CpG sites located in three genes (cg06418238 in RPTOR, cg00736299 in MGRN1 and cg27466532 in RAPSN), which showed significant hypomethylation in BC patients compared to healthy controls in the discovery cohort (p < 1.00 x 10-6) were selected and successfully validated in three independent cohorts (validation I, n =211; validation II, n=378; validation III, n=520). The observed methylation differences are likely not cell-type specific, as the differences were only seen in whole blood, but not in specific sub cell-types of leucocytes. Moreover, we observed in quartile analysis that women in the lower methylation quartiles of these three loci had higher ORs than women in the higher quartiles. The combined AUC of three loci was 0.79 (95%CI 0.73-0.85) in validation cohort I, and was 0.60 (95%CI 0.54-0.66) and 0.62 (95%CI 0.57-0.67) in validation cohort II and III, respectively. Our study suggests that hypomethylation of CpG sites in RPTOR, MGRN1 and RAPSN in blood is associated with BC and might serve as blood-based marker supplements for BC if these could be verified in prospective studies.
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000130650 7001_ $$0P:(DE-He78)457c042884c901eb0a02c18bb1d30103$$aHolland-Letz, Tim$$b1$$udkfz
000130650 7001_ $$0P:(DE-He78)4169c43af2de6fae487c89fc2e7cfaa8$$aSlynko, Alla$$b2$$udkfz
000130650 7001_ $$0P:(DE-He78)0a8ada1f5d2ea05fc3af10cd808bfa9a$$aCuk, Katarina$$b3$$udkfz
000130650 7001_ $$aMarme, Frederik$$b4
000130650 7001_ $$aSchott, Sarah$$b5
000130650 7001_ $$aHeil, Jörg$$b6
000130650 7001_ $$aQu, Bin$$b7
000130650 7001_ $$aGolatta, Michael$$b8
000130650 7001_ $$aBewerunge-Hudler, Melanie$$b9
000130650 7001_ $$aSutter, Christian$$b10
000130650 7001_ $$0P:(DE-He78)ec311cea9d07f894e44d05a570e26e28$$aSurowy, Harald$$b11$$udkfz
000130650 7001_ $$aWappenschmidt, Barbara$$b12
000130650 7001_ $$aSchmutzler, Rita$$b13
000130650 7001_ $$aHoth, Markus$$b14
000130650 7001_ $$aBugert, Peter$$b15
000130650 7001_ $$aBartram, Claus R$$b16
000130650 7001_ $$aSohn, Christof$$b17
000130650 7001_ $$aSchneeweiss, Andreas$$b18
000130650 7001_ $$0P:(DE-He78)dd35af1fb84ec0812fe4bdea97d2f291$$aYang, Rongxi$$b19$$udkfz
000130650 7001_ $$0P:(DE-He78)15b7fd2bc02d5ef47a2fe2dd0140d2bf$$aBurwinkel, Barbara$$b20$$eLast author$$udkfz
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000130650 9141_ $$y2016
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