
In our Department we investigate molecular characteristics of solid cancers, especially of the colon, rectum, pancreas and ovaries. Within these studies we focus on the molecular epidemiological level in order 1. to identify biomarkers of increased predisposition to tumour diseases, 2. enable early diagnostics, 3. assess individual responses to anti-tumour treatment, 4. and determine long-term prognosis. The Department has been working with different types of biological material from a patients with cancer diseases, such as solid tissue, blood cells or plasma.
Veronika Vymetálková, PhD.
E-mail: veronika.vymetalkova@iem.cas.cz
Phone: +420 241 062 699
Michal Kroupa, PhD.
Alessio Naccarati, PhD.
Alena Opattová, PhD.
Soňa Vodenková, PhD.
Pavel Vodička, MD, PhD.
Ludmila Vodičková, MD, PhD.
Veronika Vymetálková, PhD.
Petra Bendová, MSc
Klára Červená, MSc
Andrea Čumová, MSc
Josef Horák, MD
Alexandra Rejhová, MSc
Anna Šišková, MSc.
Kristýna Tomášová, MSc
Phone: +420 241 062 251
Jana Slyšková, PhD.
Markéta Urbanová, PhD.
Dominika Dušková
RNDr. Petr Hanák, Ph.D.
1) Genetic variations in microRNA binding sites of solute carrier transporter genes as predictors of clinical outcome in colorectal cancer
SNPs in SLCO3A1, SLC22A2, and SLC22A3 genes were defined as prognostic factors in the classification and regression tree analysis. In contrast, we did not observe any significant association between miRSNPs and CRC risk.
Overall Survival (OS) classification & regression tree analysis of colorectal cancer patients. B: Corresponding Kaplan-Meier curves represent the differences in OS stratified for each node for rs103909, rs2108601, and rs739439
Publication: Genetic variations in microRNA-binding sites of solute carrier transporter genes as predictors of clinical outcome in colorectal cancer. Bendova P, Pardini B, Susova S, Rosendorf J, Levy M, Skrobanek P, Buchler T, Kral J, Liska V, Vodickova L, Landi S, Soucek P, Naccarati A, Vodicka P, Vymetalkova V. Carcinogenesis. 2021 Apr 17;42(3):378-394. doi: 10.1093/carcin/bgaa136. PMID: 33319241
2) Researchers from the Department of Molecular Biology of Cancer are co-authors of 2 papers published in Nature Protocols
These papers have been crafted as part of long-term international cooperation, which culminated in a 4-year project hCOMET - The comet assay as a human biomonitoring tool (http://www.hcomet.eu), which was completed in autumn 2020. The hCOMET project, led by prof. Andrew Collins was funded by the COST Association (COST Action CA15132, https://www.cost.eu). The European Cooperation in Science and Technology (COST) is a pan-European intergovernmental framework that supports break-through scientific and technological developments leading to new concepts and products and thereby contribute to strengthening Europe’s research and innovation capacities.
Publication: Minimum Information for Reporting on the Comet Assay (MIRCA): recommendations for describing comet assay procedures and results. Møller P, Azqueta A, Boutet-Robinet E, Koppen G, Bonassi S, Milić M, Gajski G, Costa S, Teixeira JP, Costa Pereira C, Dusinska M, Godschalk R, Brunborg G, Gutzkow KB, Giovannelli L, Cooke MS, Richling E, Laffon B, Valdiglesias V, Basaran N, Del Bo' C, Zegura B, Novak M, Stopper H, Vodicka P, Vodenkova S, de Andrade VM, Sramkova M, Gabelova A, Collins A, Langie SAS. Nat Protoc. 2020 Dec;15(12):3817-3826. doi: 10.1038/s41596-020-0398-1. Epub 2020 Oct 26. PMID: 33106678
Publication: An optimized comet-based in vitro DNA repair assay to assess base and nucleotide excision repair activity. Vodenkova S, Azqueta A, Collins A, Dusinska M, Gaivão I, Møller P, Opattova A, Vodicka P, Godschalk RWL, Langie SAS. Nat Protoc. 2020 Dec;15(12):3844-3878. doi: 10.1038/s41596-020-0401-x. Epub 2020 Nov 16. PMID: 33199871
1) 5-fluorouracil and other fluoropyrimidines in colorectal cancer
In this complex review, we present a comprehensive review summarizing options of CRC treatment and the mechanisms of 5-FU action at the molecular level, including both anabolic and catabolic ways. The main part of this review comprises the currently known molecular mechanisms underlying the chemoresistance in CRC patients. We also focus on various 5-FU pro-drugs developed to increase the amount of circulating 5-FU and to limit toxicity.
The figure summarizes the metabolism of 5-fluorouracil and its main pro-drugs Capecitabine, Tegafur and 5′-deoxy-5-fluorouridine. On the left-hand side are depicted the anabolic pathways of their transformation into individual metabolites in the cancer cell. On the right-hand side, the catabolic pathway in the liver is represented. The figure is supplemented by the consequences caused by 5-fluorouracil active metabolites in the cancer cell.
Publication: 5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future. Vodenkova S, Buchler T, Cervena K, Veskrnova V, Vodicka P, Vymetalkova V. Pharmacol Ther. 2020 Feb;206:107447. doi: 10.1016/j.pharmthera.2019.107447.
2) Expression quantitative trait loci (eQTL) in ABC transporters are associated with survival in 5-FU treated colorectal cancer patients
In this study, we identified 14 single nucleotide polymorphisms (SNPs) in 11 ABC transporter genes acting as an expression of quantitative trait loci (eQTLs), i.e., whose variation influence the expression of many downstream genes. The rs3819720 polymorphism in the ABCB3/TAP2 gene was statistically significantly associated with shorter overall survival (OS) in the codominant, and dominant models.
Workflow of the study:
Kaplan-Meier OS curves in CRC patients stratified for rs3819720 in ABCB3/TAP2 gene
Publication: Expression quantitative trait loci in ABC transporters are associated with survival in 5-FU treated colorectal cancer patients. Vymetalkova V, Rosa F, Susova S, Bendova P, Levy M, Buchler T, Kral J, Bartu L, Vodickova L, Hughes DJ, Soucek P, Naccarati A, Kumar R, Vodicka P, Pardini B. Mutagenesis. 2020 Jul 11;35(3):273-281. doi: 10.1093/mutage/gez050. PMID: 31922572
Results of the study of 16 genetic variants of DNA repair genes:
Identification of a single genetic polymorphism (rs3204953, the REV3L gene) associated with a 2.3-fold higher risk of disease for the carriers of variant genotype (p = 0.006) in association study.
Identification of variants rs3218649 in the gene POLQ and rs7689099 in the NEIL3 gene as significantly associated with overall survival (OS) and recurrent survival (RFS), using CART analysis.
Publication : Jiraskova, K., Hughes, D., Brezina, S., Gumpenberger, T., Veskrnova, V., Buchler, T., … Vodicka, P. (2018). Functional Polymorphisms in DNA Repair Genes Are Associated with Sporadic Colorectal Cancer Susceptibility and Clinical Outcome. International Journal of Molecular Sciences, 20(1), 97. https://doi.org/10.3390/ijms20010097
Our results indicate that BER-DRC in non-malignant adjacent mucosa was positively associated with overall survival (P = 0.007) and relapse-free survival (P = 0.04). Additionally, in multivariate analysis, good therapy responders in TNM stage II and III with an elevated BER-DRC in mucosa exhibited better overall survival. Moreover, the overall survival of these patients was even better in the presence of a decreased BER-DRC in tumor tissue. The ratio of BER-DRC in tumor tissue over BER-DRC in mucosa positively correlated with advanced tumor stage (P = 0.003).
Publication : Vodenkova, S., Jiraskova, K., Urbanova, M., Kroupa, M., Slyskova, J., Schneiderova, M., … Vodicka, P. (2018). Base excision repair capacity as a determinant of prognosis and therapy response in colon cancer patients. DNA Repair, 72, 77–85. https://doi.org/10.1016/j.dnarep.2018.09.006
We identified RC-specific miRNA signature that distinguishes responders from non-responders to adjuvant chemotherapy. A predominant part of identified miRNAs was represented by the members of miR-17/92 cluster. Upregulation of miRNA-17, -18a, -18b, -19a, -19b, -20a, -20b and -106a in tumor was associated with higher risk of tumor relapse and their overexpression in RC cell lines stimulated cellular proliferation. Examination of these miRNAs in plasma exosomes showed that their levels differed between RC patients and healthy controls and correlated with patient's treatment response.
Publication : Kral, J., Korenkova, V., Novosadova, V., Langerova, L., Schneiderova, M., Liska, V., … Slyskova, J. (2018). Expression profile of miR-17/92 cluster is predictive of treatment response in rectal cancer. Carcinogenesis, 39(11), 1359–1367. https://doi.org/10.1093/carcin/bgy100
To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10−8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
Publication: Huyghe, J. R., Bien, S. A., Harrison, T. A., Kang, H. M., Chen, S., Schmit, S. L., … Peters, U. (2019). Discovery of common and rare genetic risk variants for colorectal cancer. Nature Genetics, 51(1), 76–87. https://doi.org/10.1038/s41588-018-0286-6
The CC genotype in rs8679 in PARP gene was associated with an increased risk of recurrence/progression in pacient. Carriers of at least on C allele were at a decreased risk of cancer (P = 0.005). Moreover the CC genotype in rs8679 was also associated with an increased risk of recurrence/progression in patients that received 5-FU-based chemotherapy (log-rank test P = 0.03).
Kaplan–Meier EFS curves in CRC patients undergoing 5-FU-based chemotherapy stratified for rs8679 in PARP1 gene.
Publication: Michaela Schneiderova, Alessio Naccarati, Barbara Pardini, Fabio Rosa, Cornelia Di Gaetano, Katerina Jiraskova, Alena Opattova, Miroslav Levy, Karel Veskrna, Veronika Veskrnova, Tomas Buchler, Stefano Landi, Pavel Vodicka, Veronika Vymetalkova; MicroRNA-binding site polymorphisms in genes involved in colorectal cancer etiopathogenesis and their impact on disease prognosis, Mutagenesis, Volume 32, Issue 5, 17 October 2017, Pages 533-542, https://doi.org/10.1093/mutage/gex026
We observed statistically significant increased level of chromosomal damage in CRC patients compared with controls after bleomycin treatment. Patients with shorter relative telomere length exhibited significantly higher amount of damage in peripheral lymphocytes after bleomycin treatment
Spearman correlation of relative telomere length and chromosomal damage in CRC patients and controls.
Publication: Kroupa M , Polivkova Z, Rachakonda S, et al. Bleomycin-induced chromosomal damage and shortening of telomeres in peripheral blood lymphocytes of incident cancer patients. Genes Chromosomes Cancer. 2018;57:61–69. https://doi.org/10.1002/gcc.22508
Patients carrying the CC genotype of rs886403 in MUC21 displayed a shorter survival and higher recurrence risk when compared with TT.
Publication: Veronika Vymetalkova , Barbara Pardini, Fabio Rosa, Katerina Jiraskova, Cornelia Di Gaetano, Petra Bendova, Miloslav Levy, Veronika Veskrnova, Tomas Buchler, Ludmila Vodickova, Alessio Naccarati, Pavel Vodicka; Polymorphisms in microRNA binding sites of mucin genes as predictors of clinical outcome in colorectal cancer patients, Carcinogenesis, Volume 38, Issue 1, 1 January 2017, Pages 28–39, https://doi.org/10.1093/carcin/bgw114
Analysis of methylation profile of paired samples of patient with rectal carcinoma (tumor tussue vs. adjacent mucosa) revealed aberrant methylation in 33 genes. This study has demonstrated the possibility of using specific methylated DNA profiles as diagnostic biomarkers in patients with rectal carcinoma.
Publication: Veronika Vymetalkova , Pavel Vodicka, Barbara Pardini, Fabio Rosa, Miroslav Levy, Michaela Schneiderova, Vaclav Liska, Ludmila Vodickova, Torbjörn K Nilsson, and Sanja A Farkas; Epigenome-wide analysis of DNA methylation reveals a rectal cancer-specific epigenomic signature, Epigenomics 2016 8:9, 1193-1207, https://doi.org/10.2217/epi-2016-0044
Corradi C, Gentiluomo M, Gajdán L, Cavestro GM, Kreivenaite E, Di Franco G, Sperti C, Giaccherini M, Petrone MC, Tavano F, Gioffreda D, Morelli L, Soucek P, Andriulli A, Izbicki JR, Napoli N, Małecka-Panas E, Hegyi P, Neoptolemos JP, Landi S, Vashist Y, Pasquali C, Lu Y, Cervena K, Theodoropoulos GE, Moz S, Capurso G, Strobel O, Carrara S, Hackert T, Hlavac V, Archibugi L, Oliverius M, Vanella G, Vodicka P, Arcidiacono PG, Pezzilli R, Milanetto AC, Lawlor RT, Ivanauskas A, Szentesi A, Kupcinskas J, Testoni SGG, Lovecek M, Nentwich M, Gazouli M, Luchini C, Zuppardo RA, Darvasi E, Brenner H, Gheorghe C, Jamroziak K, Canzian F, Campa D. Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility. Int J Cancer. 2021 Jun 1;148(11):2779-2788. doi: 10.1002/ijc.33475. Epub 2021 Feb 3. PMID: 33534179
Vodicka P , Andera L, Opattova A, Vodickova L. The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction. Cancers (Basel). 2021 Jan 27;13(3):479. doi: 10.3390/cancers13030479. PMID: 33513745
Kroupa M, Rachakonda S, Vymetalkova V, Tomasova K, Liska V, Vodenkova S, Cumova A, Rossnerova A, Vodickova L, Hemminki K, Soucek P, Kumar R, Vodicka P. Telomere length in peripheral blood lymphocytes related to genetic variation in telomerase, prognosis and clinicopathological features in breast cancer patients. Mutagenesis. 2020 Dec 26:geaa030. doi: 10.1093/mutage/geaa030. Online ahead of print. PMID: 33367858
Bull CJ, Bell JA, Murphy N, Sanderson E, Davey Smith G, Timpson NJ, Banbury BL, Albanes D, Berndt SI, Bézieau S, Bishop DT, Brenner H, Buchanan DD, Burnett-Hartman A, Casey G, Castellví-Bel S, Chan AT, Chang-Claude J, Cross AJ, de la Chapelle A, Figueiredo JC, Gallinger SJ, Gapstur SM, Giles GG, Gruber SB, Gsur A, Hampe J, Hampel H, Harrison TA, Hoffmeister M, Hsu L, Huang WY, Huyghe JR, Jenkins MA, Joshu CE, Keku TO, Kühn T, Kweon SS, Le Marchand L, Li CI, Li L, Lindblom A, Martín V, May AM, Milne RL, Moreno V, Newcomb PA, Offit K, Ogino S, Phipps AI, Platz EA, Potter JD, Qu C, Quirós JR, Rennert G, Riboli E, Sakoda LC, Schafmayer C, Schoen RE, Slattery ML, Tangen CM, Tsilidis KK, Ulrich CM, van Duijnhoven FJB, van Guelpen B, Visvanathan K, Vodicka P, Vodickova L, Wang H, White E, Wolk A, Woods MO, Wu AH, Campbell PT, Zheng W, Peters U, Vincent EE, Gunter MJ. Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study. BMC Med. 2020 Dec 17;18(1):396. doi: 10.1186/s12916-020-01855-9. PMID: 33327948
Bendova P , Pardini B, Susova S, Rosendorf J, Levy M, Skrobanek P, Buchler T, Kral J, Liska V, Vodickova L, Landi S, Soucek P, Naccarati A, Vodicka P, Vymetalkova V. Genetic variations in microRNA binding sites of solute carrier transporter genes as predictors of clinical outcome in colorectal cancer. Carcinogenesis. 2020 Dec 15:bgaa136. doi: 10.1093/carcin/bgaa136. Online ahead of print. PMID: 33319241
Nounu A, Greenhough A, Heesom KJ, Richmond RC, Zheng J, Weinstein SJ, Albanes D, Baron JA, Hopper JL, Figueiredo JC, Newcomb PA, Lindor NM, Casey G, Platz EA, Le Marchand L, Ulrich CM, Li CI, van Duijnhoven FJB, Gsur A, Campbell P, Moreno V, Vodicka P, Vodickova L, Brenner H, Chang-Claude J, Hoffmeister M, Sakoda LC, Slattery ML, Schoen RE, Gunter MJ, Castellví-Bel S, Kim HR, Kweon SS, Chan AT, Li L, Zheng W, Bishop DT, Buchanan DD, Giles GG, Gruber SB, Rennert G, Stadler ZK, Harrison TA, Lin Y, Keku TO, Woods MO, Schafmayer C, Van Guelpen B, Gallinger S, Hampel H, Berndt SI, Pharoah PDP, Lindblom A, Wolk A, Wu AH, White E, Peters U, Drew DA, Scherer D, Bermejo JL, Williams AC, Relton CL. A combined proteomics and Mendelian randomization approach to investigate the effects of aspirin-targeted proteins on colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2020 Dec 14:cebp.1176.2020. doi: 10.1158/1055-9965.EPI-20-1176. Online ahead of print. PMID: 33318029
Vodenkova S , Azqueta A, Collins A, Dusinska M, Gaivão I, Møller P, Opattova A, Vodicka P, Godschalk RWL, Langie SAS. An optimized comet-based in vitro DNA repair assay to assess base and nucleotide excision repair activity. Nat Protoc. 2020 Dec;15(12):3844-3878. doi: 10.1038/s41596-020-0401-x. Epub 2020 Nov 16. PMID: 33199871
Møller P, Azqueta A, Boutet-Robinet E, Koppen G, Bonassi S, Milić M, Gajski G, Costa S, Teixeira JP, Costa Pereira C, Dusinska M, Godschalk R, Brunborg G, Gutzkow KB, Giovannelli L, Cooke MS, Richling E, Laffon B, Valdiglesias V, Basaran N, Del Bo' C, Zegura B, Novak M, Stopper H, Vodicka P, Vodenkova S, de Andrade VM, Sramkova M, Gabelova A, Collins A, Langie SAS. Minimum Information for Reporting on the Comet Assay (MIRCA): recommendations for describing comet assay procedures and results. Nat Protoc. 2020 Dec;15(12):3817-3826. doi: 10.1038/s41596-020-0398-1. Epub 2020 Oct 26. PMID: 33106678 Review.
Niazi Y, Thomsen H, Smolkova B, Vodickova L, Vodenkova S, Kroupa M, Vymetalkova V, Kazimirova A, Barancokova M, Volkovova K, Staruchova M, Hoffmann P, Nöthen MM, Dusinska M, Musak L, Vodicka P, Hemminki K, Försti A. Impact of genetic polymorphisms in kinetochore and spindle assembly genes on chromosomal aberration frequency in healthy humans. Mutat Res. 2020 Oct-Dec;858-860:503253. doi: 10.1016/j.mrgentox.2020.503253. Epub 2020 Sep 15. PMID: 33198934
Guo X, Lin W, Wen W, Huyghe J, Bien S, Cai Q, Harrison T, Chen Z, Qu C, Bao J, Long J, Yuan Y, Wang F, Bai M, Abecasis GR, Albanes D, Berndt SI, Bézieau S, Bishop DT, Brenner H, Buch S, Burnett-Hartman A, Campbell PT, Castellví-Bel S, Chan AT, Chang-Claude J, Chanock SJ, Cho SH, Conti DV, de la Chapelle A, Feskens EJ, Gallinger SJ, Giles GG, Goodman PJ, Gsur A, Guinter M, Gunter MJ, Hampe J, Hampel H, Hayes RB, Hoffmeister M, Kampman E, Kang HM, Keku TO, Kim HR, Le Marchand L, Lee SC, Li CI, Li L, Lindblom A, Lindor N, Milne RL, Moreno V, Murphy N, Newcomb PA, Nickerson DA, Offit K, Pearlman R, Pharoah PDP, Platz EA, Potter JD, Rennert G, Sakoda LC, Schafmayer C, Schmit SL, Schoen RE, Schumacher FR, Slattery ML, Su YR, Tangen CM, Ulrich CM, van Duijnhoven FJ, Van Guelpen B, Visvanathan K, Vodicka P, Vodickova L, Vymetalkova V, Wang X, White E, Wolk A, Woods MO, Casey G, Hsu L, Jenkins MA, Gruber SB, Peters U, Zheng W. Identifying novel susceptibility genes for colorectal cancer risk from a transcriptome-wide association study of 125,478 subjects. Gastroenterology. 2020 Oct 12:S0016-5085(20)35243-4. doi: 10.1053/j.gastro.2020.08.062. Online ahead of print. PMID: 33058866
Vodenkova S, Kroupa M, Polivkova Z, Musak L, Ambrus M, Schneiderova M, Kozevnikovova R, Vodickova L, Rachakonda S, Hemminki K, Kumar R, Vodicka P. Chromosomal damage and telomere length in peripheral blood lymphocytes of cancer patients. Oncol Rep. 2020 Nov;44(5):2219-2230. doi: 10.3892/or.2020.7774. Epub 2020 Sep 21. PMID: 33000239
Thomas M, Sakoda LC, Hoffmeister M, Rosenthal EA, Lee JK, van Duijnhoven FJB, Platz EA, Wu AH, Dampier CH, de la Chapelle A, Wolk A, Joshi AD, Burnett-Hartman A, Gsur A, Lindblom A, Castells A, Win AK, Namjou B, Van Guelpen B, Tangen CM, He Q, Li CI, Schafmayer C, Joshu CE, Ulrich CM, Bishop DT, Buchanan DD, Schaid D, Drew DA, Muller DC, Duggan D, Crosslin DR, Albanes D, Giovannucci EL, Larson E, Qu F, Mentch F, Giles GG, Hakonarson H, Hampel H, Stanaway IB, Figueiredo JC, Huyghe JR, Minnier J, Chang-Claude J, Hampe J, Harley JB, Visvanathan K, Curtis KR, Offit K, Li L, Le Marchand L, Vodickova L, Gunter MJ, Jenkins MA, Slattery ML, Lemire M, Woods MO, Song M, Murphy N, Lindor NM, Dikilitas O, Pharoah PDP, Campbell PT, Newcomb PA, Milne RL, MacInnis RJ, Castellví-Bel S, Ogino S, Berndt SI, Bézieau S, Thibodeau SN, Gallinger SJ, Zaidi SH, Harrison TA, Keku TO, Hudson TJ, Vymetalkova V, Moreno V, Martín V, Arndt V, Wei WQ, Chung W, Su YR, Hayes RB, White E, Vodicka P, Casey G, Gruber SB, Schoen RE, Chan AT, Potter JD, Brenner H, Jarvik GP, Corley DA, Peters U, Hsu L. Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk. Am J Hum Genet. 2020 Jul 29:S0002-9297(20)30236-6. doi: 10.1016/j.ajhg.2020.07.006. Online ahead of print. PMID: 32758450
Caja F, Vodickova L, Kral J, Vymetalkova V, Naccarati A, Vodicka P. DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers. Int J Mol Sci. 2020 Aug 3;21(15):E5561. doi: 10.3390/ijms21155561. PMID: 32756484 Review.
Filip S, Vymetalkova V, Petera J, Vodickova L, Kubecek O, John S, Cecka F, Krupova M, Manethova M, Cervena K, Vodicka P. Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review. Int J Mol Sci. 2020 Jul 24;21(15):E5255. doi: 10.3390/ijms21155255. PMID: 32722130 Review.
Kral J, Kojecky V, Stepan M, Vladarova M, Zela O, Knot J, Jakovljevic M, Kralova Z, Buresova R, Grega T, Bauman D, Kotyza J, Stepanova R, Hucl T, Vodicka P, Vodickova L, Spicak J. The experience with colorectal cancer screening in the Czech Republic: the detection at earlier stages and improved clinical outcomes. Public Health. 2020 Jul 4;185:153-158. doi: 10.1016/j.puhe.2020.05.021. Online ahead of print. PMID: 32634606
Tomasova K, Cumova A , Seborova K, Horak J, Koucka K, Vodickova L, Vaclavikova R, Vodicka P. DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome. Cancers (Basel). 2020 Jun 28;12(7):E1713. doi: 10.3390/cancers12071713. PMID: 32605254
Cervena K, Siskova A , Buchler T, Vodicka P, Vymetalkova V. Methylation-Based Therapies for Colorectal Cancer. Cells. 2020 Jun 24;9(6):E1540. doi: 10.3390/cells9061540. PMID: 32599894 Review.
Galeotti AA, Gentiluomo M, Rizzato C, Obazee O, Neoptolemos JP, Pasquali C, Nentwich M, Cavestro GM, Pezzilli R, Greenhalf W, Holleczek B, Schroeder C, Schöttker B, Ivanauskas A, Ginocchi L, Key TJ, Hegyi P, Archibugi L, Darvasi E, Basso D, Sperti C, Bijlsma MF, Palmieri O, Hlavac V, Talar-Wojnarowska R, Mohelnikova-Duchonova B, Hackert T, Vashist Y, Strouhal O, van Laarhoven H, Tavano F, Lovecek M, Dervenis C, Izbéki F, Padoan A, Małecka-Panas E, Maiello E, Vanella G, Capurso G, Izbicki JR, Theodoropoulos GE, Jamroziak K, Katzke V, Kaaks R, Mambrini A, Papanikolaou IS, Szmola R, Szentesi A, Kupcinskas J, Bursi S, Costello E, Boggi U, Milanetto AC, Landi S, Gazouli M, Vodickova L, Soucek P, Gioffreda D, Gemignani F, Brenner H, Strobel O, Büchler M, Vodicka P, Paiella S, Canzian F, Campa D. Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction. J Med Genet. 2020 Jun 26:jmedgenet-2020-106961. doi: 10.1136/jmedgenet-2020-106961. Online ahead of print. PMID: 32591343
Siskova A, Cervena K , Kral J, Hucl T, Vodicka P, Vymetalkova V. Colorectal Adenomas-Genetics and Searching for New Molecular Screening Biomarkers. Int J Mol Sci. 2020 May 5;21(9). pii: E3260. doi: 10.3390/ijms21093260. Review. PubMed PMID: 32380676.
Campa D, Gentiluomo M, Obazee O, Ballerini A, Vodickova L, Hegyi P, Soucek P, Brenner H, Milanetto AC, Landi S, Gao X, Bozzato D, Capurso G, Tavano F, Vashist Y, Hackert T, Bambi F, Bursi S, Oliverius M, Gioffreda D, Schöttker B, Ivanauskas A, Mohelnikova-Duchonova B, Darvasi E, Pezzilli R, Małecka-Panas E, Strobel O, Gazouli M, Katzke V, Szentesi A, Cavestro GM, Farkas G Jr, Izbicki JR, Moz S, Archibugi L, Hlavac V, Vincze Á, Talar-Wojnarowska R, Rusev B, Kupcinskas J, Greenhalf B, Dijk F, Giese N, Boggi U, Andriulli A, Busch OR, Vanella G, Vodicka P, Nentwich M, Lawlor RT, Theodoropoulos GE, Jamroziak K, Zuppardo RA, Moletta L, Ginocchi L, Kaaks R, Neoptolemos JP, Lucchesi M, Canzian F. Genome-wide association study identifies an early onset pancreatic cancer risk locus. Int J Cancer. 2020 Apr 9. doi: 10.1002/ijc.33004. [Epub ahead of print] PubMed PMID:32270874.
Vodicka P, Urbanova M , Makovicky P, Tomasova K, Kroupa M, Stetina R, Opattova A, Kostovcikova K, Siskova A, Schneiderova M, Vymetalkova V, Vodickova L. Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients. Int J Mol Sci. 2020 Apr 2;21(7). pii: E2473. doi: 10.3390/ijms21072473. Review. PubMed PMID:32252452; PubMed Central PMCID: PMC7177219.
Tomasova K, Kroupa M , Forsti A, Vodicka P, Vodickova L. Telomere maintenance in interplay with DNA repair in pathogenesis and treatment of colorectal cancer. Mutagenesis. 2020 Feb 21. pii: geaa005. doi: 10.1093/mutage/geaa005. [Epub ahead of print] PubMed PMID: 32083302.
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Kunická, T., Václavíková, R., Hlaváč, V., Vrána, D., Pecha, V., Rauš, K., Trnková, M., Kubáčková, K., Ambruš, M., Vodičková, L., Vodička, P., Souček, P.: (2014) Non-Coding Polymorphisms in Nucleotide Binding Domain 1 in ABCC1 Gene Associate with Transcript Level and Survival of Patients with Breast Cancer. PLoS One 9(7): e101740.
Lu, S., Pardini, B., Cheng, B., Naccarati, A., Huhn, S., Vymetálková, V., Vodičková, L., Buchler, T., Hemminki, K., Vodička, P., Försti, A.: (2014) Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival. PLoS One 9(10): e111061.
Makovický, P., Tumova, E., Volek, Z., Makovický, P., Vodičková, L., Slyšková, J., Svoboda, M., Rejhová, A., Vodička, P., Samasca, G., Králová, A., Nagy, M., Mydlarova-Blascaková, M., Poracova, J.: (2014) Histopathological aspects of liver under variable food restriction: Has the intense one-week food restriction a protective effect on non-alcoholic-fatty-liver-disease (NAFLD) development?Pathol. Res. Pract. 210(12): 855-862.
Makovický, P., Tůmová, E., Volek, Z., Makovický, P., Vodička, P.: (2014) Histological aspects of the small intestine under variable feed restriction: The effects of short and intense restriction on a growing rabbit model. Exp. Ther. Med. 8(5): 1623-1627.
Pardini, B., Verderio, P., Pizzamiglio, S., Nici, C., Maiorana, M. V., Naccarati, A., Vodičková, L., Vymetálková, V., Veneroni, S., Daidone, M. G., Ravagnani, F., Bianchi, T., Bujenda, L., Carracedo, A., Castells, A., Ruiz-Ponte, C., Morreau, H., Howarth, K., Jones, A., Castellvı´-Bel, S., Li L., Tomlinson, I., Van Wezel, T., Vodička, P., Radice, P., Peterlongo, P., the EPICOLON Consortium: (2014) Association between CASP8 –652 6N Del Polymorphism (rs3834129) and Colorectal Cancer Risk: Results from a Multi-Centric Study. PLoS ONE 9(3): e91310.
Pardini, B., Bermejo, J. L., Naccarati, A., Di Gaetano, C., Rosa, F., Legrand, C., Novotny, J., Vodička, P., Kumar, R.: (2014) Inherited variability in a master regulator polymorphism (rs4846126) associates with survival in 5-FU treated colorectal cancer patients.Mutat. Res.-Fundam. Mol. Mech. Mutagen. 766-767: 7-13.
Svoboda, M., Slyšková, J., Schneiderova, M., Makovicky, P., Bielik, L., Levy, M., Lipska, L., Hemmelova, B., Kala, Z., Protivankova, M., Vycital, O., Liska, V., Schwarzova, L., Vodičková, L, Vodička P.: (2014) HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients. Carcinogenesis. 35(7): 1510-1515.
Slyšková, J., Lorenzo, Y., Karlsen, A., Carlsen, M. H., Novosadová, V., Blomhoff, R., Vodička, P., Collins, A. R.: (2014) Both genetic and dietary factors underlie individual differences in DNA damage levels and DNA repair capacity. DNA Repair (Amst). 16 :66-73.
Slyšková, J., Langie, S, A. , Collins, A. R., Vodička, P.: (2014) Functional evaluation of DNA repair in human biopsies and their relation to other cellular biomarkers. Front Genet. 5: 116.
Švec, J., Schwarzová, L., Janošíková, B., Štekrová, J., Mandys, V., Kment, M., Vodička, P.: (2014) Synchronous gastric and sebaceous cancers, a rare manifestation of MLH1-related Muir-Torre syndrome. Int. J. Clin. Exp. Pathol. 7(8): 5196-5202.
Vymetálková, V., Pardini, B., Rosa, F., Di Gaetano, C., Novotny, J., Levy, M., Buchler, T., Slyšková, J., Vodičková, L., Naccarati, A., Vodička, P.: (2014) Variations in mismatch repair genes and colorectal cancer risk and clinical outcome. Mutagenesis. 29(4): 259-265.
Vymetálková, V., Slyšková, J., Korenková, V., Bielik, L., Langerová, L., Procházka, P., Rejhová, A., Schwarzová, L., Pardini, B.,Naccarati, A., Vodička, P.: (2014) Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients BMC Med. Genet. 15(1) :17.
Wolpin, B. M., Rizzato, C., Kraft, P., Kooperberg, C., Petersen, G. M., Wang, Z., Arslan, A. A., Beane-Freeman, L., Bracci, P.M., Buring, J., Canzian, F., Duell, E. J., Gallinger, S., Giles, G. G., Goodman, G. E., Goodman, P. J., Jacobs, E. J., Kamineni, A., Klein, A. P., Kolonel, L. N., Kulke, M. H., Li, D., Malats, N., Olson, S. H., Risch, H. A., Sesso, H. D., Visvanathan, K., White, E., Zheng, W., Abnet, C. C., Albanes, D., Andreotti, G., Austin, M. A., Barfield, R., Basso, D., Berndt, S. I., Boutron-Ruault, M. C., Brotzman, M., Büchler, M. W., Bueno-de-Mesquita, H. B., Bugert, P., Burdette, L., Campa, D., Caporaso, N. E., Capurso, G., Chung, C., Cotterchio, M., Costello, E., Elena, J., Funel, N., Gaziano, J. M., Giese, N. A., Giovannucci, E. L., Goggins, M., Gorman, M. J., Gross, M., Haiman, C. A., Hassan, M., Helzlsouer, K. J., Henderson, B. E., Holly, E. A., Hu, N., Hunter, D. J., Innocenti, F., Jenab, M., Kaaks, R., Key, T. J., Khaw, K. T., Klein, E. A., Kogevinas, M., Krogh, V., Kupcinskas, J., Kurtz, R. C., LaCroix, A., Landi, M. T., Landi, S., Le Marchand, L., Mambrini, A., Mannisto, S., Milne, R. L., Nakamura, Y., Oberg, A. L., Owzar, K., Patel, A. V., Peeters, P. H., Peters, U., Pezzilli, R., Piepoli, A., Porta, M., Real, F. X., Riboli, E., Rothman, N., Scarpa, A., Shu, X. O., Silverman, D. T., Soucek, P., Sund, M., Talar-Wojnarowska, R., Taylor, P. R., Theodoropoulos, G. E., Thornquist, M., Tjønneland, A., Tobias, G. S., Trichopoulos, D., Vodička, P., Wactawski-Wende, J., Wentzensen, N., Wu, C., Yu, H., Yu, K., Zeleniuch-Jacquotte, A., Hoover, R., Hartge, P., Fuchs, C., Chanock, S. J., Stolzenberg-Solomon, R. S., Amundadottir, L. T.: (2014) Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nature Genet. 46(9): 994-1000.
Azqueta, A., Langie, S. A., Slyšková, J., Collins, A. R.: (2013) Measurement of DNA base and nucleotide excision repair activities in mammalian cells and tissues using the comet assay - A methodological overview. DNA Repair (Amst) 12: 1007-1010.
Campa, D., Rizzato, C., Capurso, G., Giese, N., Funel, N., Greenhalf, W., Souček, P., Gazouli, M., Pezzilli, R, Pasquali, C., Talar-Wojnarowska, R., Cantore, M., Andriulli, A., Scarpa, A., Jamroziak, K., Delle Fave, G., Costello, E., Khaw, K. T., Heller, A., Key, T. J., Theodoropoulos, G., Malecka-Panas, E., Mambrini, A., Bambi, F., Land, S., Pedrazzoli, S., Bassi, C., Pacetti, P., Piepoli, A., Tavano, F., di Sebastiano, P., Vodičková, L., Basso, D., Plebani, M., Fogar, P., Büchler, M. W., Bugert, P., Vodička, P., Boggi, U., Neoptolemos, J. P., Werner, J., Canzian, F.: (2013) Genetic susceptibility to pancreatic cancer and its functional characterisation: The PANcreatic Disease ReseArch (PANDoRA) consortium. Dig. Liver Dis. 45(2): 95-99.
Campa, D., Rizzato, C., Bauer, A. S., Werner, J., Capurso, G., Costello, E., Talar-Wojnarowska, R., Jamroziak, K., Pezzilli, R., Gazouli, M., Khaw, K. T., Key, T. J., Bambi, F., Mohelnikova-Duchonova, B., Heller, A., Landi, S., Vodičková, L., Theodoropoulos, G., Bugert, P.,Vodička, P., Hoheisel, J., Delle Fave, G., Neoptolemos, J., Souček, P., Buchler, M. W., Giese, N. A., Canzian F.: (2013) Lack of replication of seven pancreatic cancer susceptibility lociidentified in two Asian populations. Cancer Epidemiol. Biomarkers Prev.22(2): 320-323.
Lu, S., Bevier, M., Huhn, S., Sainz, J., Lascorz, J., Pardini, B., Naccarati, A., Vodičková, L., Novotný, J., Hemminki, K., Vodička, P., Försti A.: (2013) Genetic variants in C-type lectin genes are associated with colorectal cancer susceptibility and clinical outcome.Int. J. Cancer. 133(10): 2325-2333.
Makovicky, P., Rimarova, K., Boor, A., Makovicky, P., Vodička, P., Samasca, G., Kruzliak, P.: (2013) Correlation between antibodies and histology in celiac disease: Incidence of celiac disease is higher than expected in the pediatric population. Mol. Med. Rep.8(4): 1079-1083.
Mušák, L., Šmerhovský, Z., Halasová, E., Osina, O., Letková, L., Vodičková, L., Poláková, V., Buchancová, J., Hemminki, K.,Vodička, P.: (2013) Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde. Scand. J. Work Environ. Health. 39(6): 618-630.
Pardini, B., Rosa, F., Barone, E., Di Gaetano, C., Slyšková, J., Novotný, J., Levy, M., Garritano, S., Vodičková, L., Buchler, T., Gemignani, F., Landi, S., Vodička, P., Naccarati, A.: (2013) Variation within 3' UTRs of base excision repair genes and response to therapy in colorectal cancer patients: a potential modulation of microRNAs binding. Clin. Cancer Res. 19(21): 6044-6056.
Picelli, S., Bermejo, J. L., Change-Claude, J., Hoffmeister, M., Fernández-Rozadilla, C., Carracedo, A., Castells, A., Castellví-Bel, S.,Naccarati, A., Pardini, B., Vodičková, L., Hüller, H., Talseth-Palmer, B. A., Stibbard, G., Peterlongo, P., Nici, C., Veneroni, S., Li, L., Casey, G., Tenesa, A., Farrington, S. M., Tomlinson, I., Moreno, V., van Wezel, T., Wijnen, J., Dunlop, M., Radice, P., Scott, R. J.,Vodička, P., Ruiz-Ponte, C., Brenner, H., Buch, S., Völzke, H., Hampe, J., Schafmayer, C., Lindblom, A.: Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility; PLoS One 8(9): e72091.
Poláková-Vymetálková, V., Vannucci, L., Korenková, V., Procházka, P., Slyšková, J., Vodičková, L., Rusňáková, V., Bielik, L., Burocziová, M., Rossmann., P., Vodička, P.: (2013) Evaluation of tumor suppressor gene expressions and aberrant methylation in the colon of cancer-induced rats: a pilot study. Mol. Biol. Rep. 40(10): 5921-5929.
Procházka, P., Hrabeta, J., Vicha, A., Cipro, S., Stejskalová, E., Musil, Z., Vodička, P., Eckschlager, T.: (2013) Changes in MYCN expression in human neuroblastoma cell lines following cisplatin treatment may not be related to MYCN copy numbers. Oncol. Rep. 29(6):2415-2421.
Rizzato, C., Campa, D., Pezzilli, R., Souček, P., Greenhalf, W., Capurso, G., Talar-Wojnarowska, R., Heller, A., Jamroziak, K., Khaw, K. T., Key, T. J., Bambi, F., Landi, S., Mohelniková-Duchoňová, B., Vodičková, L., Büchler, M. W., Bugert. P., Vodička, P., Neoptolemos, J. P., Werner, J., Hoheisel, J. D., Bauer, A. S., Giese, N., Canzian, F.: (2013) ABO blood groups and pancreatic cancer risk and survival: Results from the PANcreatic Disease ReseArch (PANDoRA) consortium. Oncol. Rep. 29(4): 1637-1644.
AZV 17-30920A Characterization of acquired chemoresistance by DNA repair gene profiling in colon cancer patients through non-invasive repeated analysis. PI: Ing. Vymetálková, (2017-2020).
GACR 18- 09709S Mapping the traits involved in malignant transformation of colorectal adenoma into carcinoma. PI: Dr. Vodička, (2018-2020).
NV 18-03-00199 Identification of diagnostic markers in colorectal cancer by profiling of trascriptome, DNA methylome and microbiome in adenoma-carcinoma transition. PI: Dr. Vodička, (2018-2021).
GACR 19-10543S Changes in DNA repair system associated with therapy outcome of ovarian carcinoma. PI: Dr. Vodička, (2019-2021).
NV19-09-00237 The clinicopathological and molecular factors detected in metastases, predicting of treatment response in colon cancer patients. PI: Dr.Vymetálková, (2019-2022).
GACR 20-03997S Influence of microbial metabolites and diet on genome and epigenoma in colorectal carcinoma PI: Dr. Vodička, (2020-2022)
GAČR Expro: 21-04607X Horizontal transfer of mitochondria in cancer biology. PI: Dr. Vodička, (2021- 2025)
AZV NU21-03-00145 Homeostáza telomér jako potencialni biomarker rizika, prognózy a progrese u gynekologických nádorů. PI: Dr. Vodičková (2021-2024)
AZV NU21-07-00247 Využití konceptu tekuté biopsie pro charakterizaci mikroRNA a onkogenní KRAS mutace pro stanovení včasné diagnózy a zhodnocení rizika vzniku karcinomu pankreatu. PI: Dr. Vodička (2021-2024)
AZV NU21-03-00506 Význam mutačního spektra nádorových buněk ve vývoji kolorektálního karcinomu. PI: Dr. Vodička (2021-2024)
Thomayer hospital Prague
IKEM, Prague
General teaching hospital, Prague
Teaching hospital Pilsen, Pilsen
Teaching hospital Kralovske Vinohrady, Prague
Masaryk University, Brno
First Medical Faculty, Charles University, Prague
Third Medical Faculty, Charles University, Prague
Biomedical Centre, Faculty of Medicine, Pilsen, Charles University, Prague
National Institute of Public Health, Prague
Institute of Biotechnology, CAS v.v.i., Vestec
Institute of Molecular Genetics, ASCR, Prague
Institute of Microbiology, ASCR, Prague
CEITEC - central european institute of technology, Brno
DKFZ (German Cancer Research Center) Heidelberg, Germany (prof. Hemminki, prof. Kumar, Dr. Canzian, Dr. Főrsti)
University of Pisa, Italy (prof. Landi, prof. Barale, dr. Campa)
Italian Institute for Genomic Medicine, Torino, Italy (Dr. Naccarati, Dr. Pardini)
Leiden University Medical Center, Leiden, Holland (prof. Van Wezel)
IDIBAPS / CIBERehd / Hospital Clínic, Barcelona, Spain (Dr. Castellvi-Bel)
Umeå University, Sweden (Prof. Torbjőrn Nilsson)
Vienna Medical University, Austria (prof. Knasműller, Dr.Gsur)
RCSI Royal College of Surgeons in Ireland, Ireland (Dr. Hughes)
Genetics and Epidemiology of Colorectal cancer Consortium (GECCO)
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