Department of the Molecular Biology of Cancer

To date, more than 150 human DNA repair genes have been identified, which can be categorized into 5 main pathways: base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), doublestrand break repair (DSB) and direct repair. The cell cycle and mitotic spindle checkpoints are also critical in this process to ensure that cell proliferation only follows the correct replication and organization of genetic material, respectively. Otherwise, if genetic material is altered, it can be repaired at the DNA level, enabling the cell to replicate. If the genetic damage is too excessive for repair, the cell avoids propagating the damaged DNA by undergoing apoptosis. Thus DNA repair plays an important role in close relationship with cell cycle control in cancer prevention, by removing potentially mutagenic lesions and maintaining chromosomal and genomic stability. DNA repair capacity measurement represents a complex marker integrating polymorphisms, gene expression, the stability of the gene product, the effect of inhibitors/stimulators, environmental factors and lifestyle factors. In sporadic cancers, greatly affected by gene-environment interactions, the employment of new and pathway-specific DNA repair assays hallmarks cancer risk identification and the prediction of therapeutical outcome.

Stages of colorectal cancer (source: National Cancer Institute).

Current grant support

GA CR, 310/07/1430, Molecular and genetic characteristics of sporadic colorectal cancer in the Czech Republic, 2007–2011.

IGA NR, 8563-5/2005, Genetic profile of xenobiotic metabolising and DNA repair genes in cancer patients and control individuals in the Czech Republic, 2005–2009.

IGA NR, 9423-3/2007, XME, DNA repair and cell cycle regulation genes in head and neck cancer prediction, 2007–2009.

IGA NR, 9422-3/2007, The influence of environmental and genetic factors of pancreatic cancer (genetic profile), 2007–2009.

GA AS CR, IAA 500 200 917, Genetic and immunity in early stages of colorectal adenocarcinoma: inflammatory environment in conventional vs germ-free animal models, and in human samples, 2009–2013.

EEA-researchfund, A/CZ0046/2/0012, Quality and safety of food in relation to colorectal cancer predisposition. A pilot study. 2009–2010.

GA AS CR, IAA 500 390 806, The determination of expression levels of DNA repair and cell cycle genes in peripheral blood lymphocytes in styrene exposed individuals, 2008–2010.

Selected recent publications

1. Vodička P, Kumar R, Štětina R, Sanyal S, Souček P, Haufroid V, Dusinska M, Kuricová M, Zámečníková M, Musak L, Buchancová J, Norppa H, Hirvonen A, Vodičková L, Naccarati A, Matoušů Z, Hemminki K. (2004) Genetic polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and single-strand breaks in DNA. Carcinogenesis 25(5): 757–763.

2. Vodička P, Tuimala J, Štětina R, Kumar R, Manini P, Naccarati A, Maestri L, Vodičková L, Kuricová M, Järventaus H, Majvaldová Z, Hirvonen A, Imbriani M, Mutti A, Migliore L, Norppa H, Hemminki K. (2004) Cytogenetic markers, DNA single-strand breaks, urinary metabolites, and DNA repair rates in styrene-exposed lamination workers. Environ Health Perspect 112(8): 867–871.

3. Vodička P, Koskinen M, Naccarati A, Oesch-Bartlomowicz B, Vodičková L, Hemminki K, Oesch F. (2006) Styrene metabolism, genotoxicity, and potential carcinogenicity. Drug Metab Rev 38(4): 805–853.

4. Vodička P, Štětina R, Poláková V, Tulupová E, Naccarati A, Vodičková L, Kumar R, Hánová M, Pardini B, Slyšková J, Musak L, DePalma G, Souček P, Hemminki K. (2007) Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects. Carcinogenesis 28(3): 657–664. PDF file (115 kB)

5. Tomlinson IPM, Webb E, Carvajal-Carmona L, Broderick P, Howarth K, Pittman AM, Spain S, Lubbe S, Walther A, Sullivan K, Jaeger E, Fielding S, Rowan A, Vijayakrishnan J, Domingo E, Chandler I, Kemp Z, Qureshi M, Farrington SM, Tenesa A, Prendergast JGD, Barnetson RA, Penegar S, Barclay E, Wood W, Martin L, Gorman M, Thomas H, Peto J, Bishop DT, Gray R, Maher RE, Lucassen A, Kerr D, Evans DGR, Consortium the CORGI, Schafmayer C, Buch S, Völzke H, Hampe J, Schreiber S, John U, Koessler T, Pharoah P, van Wezel T, Morreau H, Wijnen J T, Hopper JL, Southey MC, Giles GG, Severi G, Castelví-Bel S, Ruiz-Ponte C, Carracedo A, Castells A, Consortium the EPICOLON, Försti A, Hemminki K, Vodička P, Naccarati A, Lipton L, Ho JWC, Cheng KK, Sham PC, Luk J, Agúndez JAG, Ladero JM, de la Hoya M, Caldés T, Niittymäki I, Tuupanene S, Karhu A, Aaltonen L, Cazier JB, Campbell H, Dunlop MG, Houlston RS. (2008) A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23. 3. Nature Genet 40(5): 623–630. PDF file (344 kB)

6. Pittman AM, Webb E, Carvajal-Carmona L, Howarth K, Di Bernardo MC, Broderick P, Spain S, Walther A, Price A, Sullivan K, Twiss P, Fielding S, Rowan A, Jaeger E, Vijayakrishnan J, Chandler I, Penegar S, Qureshi M, Lubbe S, Domingo E, Kemp Z, Barclay E, Wood W, Martin L, Gorman M, Thomas H, Peto J, Bishop T, Gray R, Maher ER, Lucassen A, Kerr D, Evans GR, CORGI Consortium, van Wezel T, Morreau H, Wijnen JT, Hopper JL, Southey MC, Giles GG, Severi G, Castellví-Bel S, Ruiz-Ponte C, Carracedo A, Castells A, EPICOLON Consortium, Försti A, Hemminki K, Vodička P, Naccarati A, Lipton L, Ho J. W, Cheng KK, Sham PC, Luk J, Agúndez JA, Ladero JM, de la Hoya M, Caldés T, Niittymäki I, Tuupanen S, Karhu A, Aaltonen LA, Cazier JB, Tomlinson IP, Houlston RS. (2008) Refinement of the basis and impact of common 11q23. 1 variation to the risk of developing colorectal cancer. Hum Mol Genet 17(23): 3720–3727. PDF file (321 kB)

7. Poláková V, Pardini B, Naccarati A, Landi S, Slyšková J, Novotný J, Vodičková L, Bermejo JL, Hánová M, Šmerhovský Z, Tulupová E, Kumar R, Hemminki K, Vodička P. (2009) Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. Hum Mutat 30(4): 661–668. PDF file (189 kB)

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