Lung Cancer Genomics/Epigenomics
PD Dr. Angela Risch
High Throughput Genotyping by Lightcycler Melting Curve Analysis (upper) and MALDI-TOF mass spectrometry using MassARRAY (lower)
© dkfz.de
Xenobiotic metabolism of environmental carcinogens and DNA-repair processes are two important ways in which individual susceptibility to environmental carcinogenesis can be affected.
Genetic polymorphisms in enzymes involved either in detoxification of procarcinogens, such as CYPs, GSTs and NATs or in repair of DNA-damage incurred as a result of exposure, may affect cancer susceptibility.
At-risk genotypes can therefore be used as susceptibility markers, with the aim of identifying high risk individuals.
The better characterization of the relevance of gene-environment interactions in the context of human carcinogenesis is of great importance for preventive measures such as the setting of exposure threshold values, public health campaigns, and chemopreventive approaches.
Major Research Directions:
- Molecular epidemiology studies investigating the modification of individual risk associated with tobacco carcinogen exposure by genetic polymorphisms
- Characterisation of the relevance of new genetic polymorphisms and further susceptibility genes for cancer
- To identify risk groups in the population for prevention and screening and
- to further add to our understanding of gene - environment interactions
- Investigation of genetic polymorphisms as possible modifiers for treatment outcome in cancer patients
Selected References:
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 May 4 (epub ahead of print)
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.