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High Throughput Genotyping by Lightcycler Melting Curve Analysis (upper) and MALDI-TOF mass spectrometry using MassARRAY (lower)
Lung Cancer is a common disease with bad treatment outcome. The main environmental risk factor clearly is tobacco smoke exposure, however, individual susceptibility to lung carcinogenesis varies. Our interdisciplinary workgroup is interested in genetic and epigenetic factors that modify both lung cancer risk (gene-environment interaction) and treatment outcome (pharmacogenetics).
We employ melting curve analysis and real-time PCR analysis using the LightCycler 480 for single nucleotide polymorphism (SNP) and copy number (CNV) genotyping, as well as the MassARRAY platform (Sequenom), for high throughput quantitative methylation-, CNV- and SNP-analyses. Genome-wide methylation analyses using tiling arrays, expression- and functional studies are also performed.
From a long-standing collaboration with the Thoraxklinik Heidelberg we have an extensive biospecimen collection with associated exposure and clinical data for molecular epidemiological risk analyses (case-control study) and translational pharmaco(epi)genetic investigations (treatment response).
We are active in the International Lung Cancer Consortium (ILCCO).
Epigenetic and genetic analyses relating to lung cancer risk and treatment outcome in lung cancer patients, with a particular focus on
Scherf DB, Dally H, Müller P, Werle-Schneider G, Jäger B, Edler L, Tuengerthal S, Fischer JR, Drings P, Bartsch H, Risch A. SNPs in matrix metalloproteinase genes and lung cancer chemotherapy response and prognosis. Eur Respir J. 2009;
Timofeeva M, Kropp S, Sauter W, Beckmann L, Rosenberger A, Illig T, Jäger B, Mittelstrass K, Dienemann H; The LUCY-Consortium, Bartsch H, Bickeböller H, Chang-Claude J, Risch A, Wichmann HE. CYP 450 polymorphisms as risk factors for early onset lung cancer: gender specific differences. Carcinogenesis 2009; 30(7): 1161-9.
Timofeeva M, Jäger B, Rosenberger A, Sauter W, Wichmann HE; KORA Study Group, Bickeböller H, Risch A. A multiplex real-time PCR method for detection of GSTM1 and GSTT1 copy numbers. Clin Biochem. 2009; 42(6): 500-9.
Müller PJ, Dally H, Klappenecker CN, Edler L, Jäger B, Gerst M, Spiegelhalder B, Tuengerthal S, Fischer JR, Drings P, Bartsch H, Risch A. Polymorphisms in ABCG2, ABCC3 and CNT1 genes and their possible impact on chemotherapy outcome of lung cancer patients. Int J Cancer 2009; 124(7): 1669-74.
Sauter W, Rosenberger A, Beckmann L, Kropp S, Mittelstrass K, Timofeeva M, Wölke G, Steinwachs A, Scheiner D, Meese E, Sybrecht G, Kronenberg F, Dienemann H; The LUCY-Consortium, Chang-Claude J, Illig T, Wichmann HE, Bickeböller H, Risch A. Matrix Metalloproteinase 1 (MMP1) Is Associated with Early-Onset Lung Cancer. Cancer Epidemiol Biomarkers Prev. 2008; 17(5): 1127-1135.
Mittelstrass K, Sauter W, Rosenberger A, Illig T, Timofeeva M, Klopp N, Dienemann H, Meese E, Sybrecht G, Woelke G, Cebulla M, Degen M, Morr H, Drings P, Groeschel A, Kreymborg KG, Haeussinger K, Hoeffken G, Schmidt C, Jilge B, Schmidt W, Ko YD, Taeuscher D, Chang-Claude J, Wichmann HE, Bickeboeller H, Risch A. Early onset lung cancer, cigarette smoking and the SNP309 of the murine double minute-2 (MDM2) gene. BMC Cancer 2008; 8: 113.
Risch A, Plass C. Lung cancer epigenetics and genetics. Int J Cancer 2008; 123(1): 1-7.
Bartsch H, Dally H, Popanda O, Risch A, Schmezer P. Genetic risk profiles for cancer susceptibility and therapy response. Recent Results Cancer Res. 2007; 174:19-36. Review.
Cox A, Dunning AM, Garcia-Closas M, Balasubramanian S, Reed MW, Pooley KA, Scollen S, Baynes C, Ponder BA, Chanock S, Lissowska J, Brinton L, Peplonska B, Southey MC, Hopper JL, McCredie MR, Giles GG, Fletcher O, Johnson N, dos Santos Silva I, Gibson L, Bojesen SE, Nordestgaard BG, Axelsson CK, Torres D, Hamann U, Justenhoven C, Brauch H, Chang-Claude J, Kropp S, Risch A, Wang-Gohrke S, Schürmann P, Bogdanova N, Dörk T, Fagerholm R, Aaltonen K, Blomqvist C, Nevanlinna H, Seal S, Renwick A, Stratton MR, Rahman N, Sangrajrang S, Hughes D, Odefrey F, Brennan P, Spurdle AB, Chenevix-Trench G; Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer, Beesley J, Mannermaa A, Hartikainen J, Kataja V, Kosma VM, Couch FJ, Olson JE, Goode EL, Broeks A, Schmidt MK, Hogervorst FB, Van't Veer LJ, Kang D, Yoo KY, Noh DY, Ahn SH, Wedrén S, Hall P, Low YL, Liu J, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Sigurdson AJ, Stredrick DL, Alexander BH, Struewing JP, Pharoah PD, Easton DF; Breast Cancer Association Consortium. A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet. 2007; 39(3): 352-8.
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