Schirmer, Markus Anton

[["dc.bibliographiccitation.firstpage","2805"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Leu, Martin"],["dc.contributor.author","Riebeling, Theresa"],["dc.contributor.author","Dröge, Leif Hendrik"],["dc.contributor.author","Hubert, Laura"],["dc.contributor.author","Guhlich, Manuel"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Rieken, Stefan"],["dc.contributor.author","Schirmer, Markus Anton"],["dc.date.accessioned","2021-07-05T15:00:42Z"],["dc.date.available","2021-07-05T15:00:42Z"],["dc.date.issued","2021"],["dc.description.abstract","Despite excellent loco-regional control by multimodal treatment of locally advanced rectal cancer, a substantial portion of patients succumb to this disease. As many treatment effects are mediated via reactive oxygen species (ROS), we evaluated the effect of single nucleotide polymorphisms (SNPs) in ROS-related genes on clinical outcome. Based on the literature, eight SNPs in seven ROS-related genes were assayed. Eligible patients (n = 287) diagnosed with UICC stage II/III rectal cancer were treated multimodally starting with neoadjuvant radiochemotherapy (N-RCT) according to the clinical trial protocols of CAO/ARO/AIO-94, CAO/ARO/AIO-04, TransValid-A, and TransValid-B. The median follow-up was 64.4 months. The Ser326Cys polymorphism in the human OGG1 gene affected clinical outcome, in particular cancer-specific survival (CSS). This effect was comparable in extent to the ypN status, an already established strong prognosticator for patient outcome. Homozygous and heterozygous carriers of the Cys326 variant (n = 105) encountered a significantly worse CSS (p = 0.0004 according to the log-rank test, p = 0.01 upon multiple testing adjustment). Cox regression elicited a hazard ratio for CSS of 3.64 (95% confidence interval 1.70–7.78) for patients harboring the Cys326 allele. In a multivariable analysis, the effect of Cys326 on CSS was preserved. We propose the genetic polymorphism Ser326Cys as a promising biomarker for outcome in rectal cancer."],["dc.description.abstract","Despite excellent loco-regional control by multimodal treatment of locally advanced rectal cancer, a substantial portion of patients succumb to this disease. As many treatment effects are mediated via reactive oxygen species (ROS), we evaluated the effect of single nucleotide polymorphisms (SNPs) in ROS-related genes on clinical outcome. Based on the literature, eight SNPs in seven ROS-related genes were assayed. Eligible patients (n = 287) diagnosed with UICC stage II/III rectal cancer were treated multimodally starting with neoadjuvant radiochemotherapy (N-RCT) according to the clinical trial protocols of CAO/ARO/AIO-94, CAO/ARO/AIO-04, TransValid-A, and TransValid-B. The median follow-up was 64.4 months. The Ser326Cys polymorphism in the human OGG1 gene affected clinical outcome, in particular cancer-specific survival (CSS). This effect was comparable in extent to the ypN status, an already established strong prognosticator for patient outcome. Homozygous and heterozygous carriers of the Cys326 variant (n = 105) encountered a significantly worse CSS (p = 0.0004 according to the log-rank test, p = 0.01 upon multiple testing adjustment). Cox regression elicited a hazard ratio for CSS of 3.64 (95% confidence interval 1.70–7.78) for patients harboring the Cys326 allele. In a multivariable analysis, the effect of Cys326 on CSS was preserved. We propose the genetic polymorphism Ser326Cys as a promising biomarker for outcome in rectal cancer."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/cancers13112805"],["dc.identifier.pii","cancers13112805"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87886"],["dc.language.iso","en"],["dc.notes.intern","DOI Import DOI-Import GROB-441"],["dc.publisher","MDPI"],["dc.relation.eissn","2072-6694"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","8-Oxoguanine DNA Glycosylase (OGG1) Cys326 Variant: Increased Risk for Worse Outcome of Patients with Locally Advanced Rectal Cancer after Multimodal Therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5585"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Guhlich, Manuel"],["dc.contributor.author","Hubert, Laura"],["dc.contributor.author","Mergler, Caroline Patricia Nadine"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Dröge, Leif Hendrik"],["dc.contributor.author","Leu, Martin"],["dc.contributor.author","Schmidberger, Heinz"],["dc.contributor.author","Rieken, Stefan"],["dc.contributor.author","Hille, Andrea"],["dc.contributor.author","Schirmer, Markus Anton"],["dc.contributor.editor","Urbanucci, Alfonso"],["dc.date.accessioned","2022-01-11T14:07:50Z"],["dc.date.available","2022-01-11T14:07:50Z"],["dc.date.issued","2021"],["dc.description.abstract","Genetic variability in transforming growth factor beta pathway (TGFB) was suggested to affect adverse events of radiotherapy. We investigated comprehensive variability in TGFB1 (gene coding for TGFβ1 ligand) and TGFBR1 (TGFβ receptor-1) in relation to radiotoxicity. Prostate cancer patients treated with primary radiotherapy (n = 240) were surveyed for acute and late toxicity. Germline polymorphisms (n = 40) selected to cover the common genetic variability in TGFB1 and TGFBR1 were analyzed in peripheral blood cells. Human lymphoblastoid cell lines (LCLs) were used to evaluate a possible impact of TGFB1 and TGFBR1 genetic polymorphisms to DNA repair capacity following single irradiation with 3 Gy. Upon adjustment for multiplicity testing, rs10512263 in TGFBR1 showed a statistically significant association with acute radiation toxicity. Carriers of the Cytosine (C)-variant allele (n = 35) featured a risk ratio of 2.17 (95%-CI 1.41–3.31) for acute toxicity ≥ °2 compared to Thymine/Thymine (TT)-wild type individuals (n = 205). Reduced DNA repair capacity in the presence of the C-allele of rs10512263 might be a mechanistic explanation as demonstrated in LCLs following irradiation. The risk for late radiotoxicity was increased by carrying at least two risk genotypes at three polymorphic sites, including Leu10Pro in TGFB1. Via comprehensive genotyping of TGFB1 and TGFBR1, promising biomarkers for radiotoxicity in prostate cancer were identified."],["dc.description.abstract","Genetic variability in transforming growth factor beta pathway (TGFB) was suggested to affect adverse events of radiotherapy. We investigated comprehensive variability in TGFB1 (gene coding for TGFβ1 ligand) and TGFBR1 (TGFβ receptor-1) in relation to radiotoxicity. Prostate cancer patients treated with primary radiotherapy (n = 240) were surveyed for acute and late toxicity. Germline polymorphisms (n = 40) selected to cover the common genetic variability in TGFB1 and TGFBR1 were analyzed in peripheral blood cells. Human lymphoblastoid cell lines (LCLs) were used to evaluate a possible impact of TGFB1 and TGFBR1 genetic polymorphisms to DNA repair capacity following single irradiation with 3 Gy. Upon adjustment for multiplicity testing, rs10512263 in TGFBR1 showed a statistically significant association with acute radiation toxicity. Carriers of the Cytosine (C)-variant allele (n = 35) featured a risk ratio of 2.17 (95%-CI 1.41–3.31) for acute toxicity ≥ °2 compared to Thymine/Thymine (TT)-wild type individuals (n = 205). Reduced DNA repair capacity in the presence of the C-allele of rs10512263 might be a mechanistic explanation as demonstrated in LCLs following irradiation. The risk for late radiotoxicity was increased by carrying at least two risk genotypes at three polymorphic sites, including Leu10Pro in TGFB1. Via comprehensive genotyping of TGFB1 and TGFBR1, promising biomarkers for radiotoxicity in prostate cancer were identified."],["dc.identifier.doi","10.3390/cancers13215585"],["dc.identifier.pii","cancers13215585"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97876"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.publisher","MDPI"],["dc.relation.eissn","2072-6694"],["dc.rights","Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)."],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Identification of Risk Loci for Radiotoxicity in Prostate Cancer by Comprehensive Genotyping of TGFB1 and TGFBR1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]