Functional Polymorphisms in DNA Repair Genes Are Associated with Sporadic Colorectal Cancer Susceptibility and Clinical Outcome

0508392 - ÚEM 2020 RIV CH eng J - Journal Article
Jirásková, Kateřina - Hughes, D. J. - Březina, S. - Gumpenberger, T. - Veškrnová, V. - Buchler, T. - Schneiderová, B. - Levý, M. - Liška, V. - Vodenková, Soňa - Di Gaetano, C. - Naccarati, Alessio - Pardini, B. - Vymetálková, Veronika - Gsur, A. - Vodička, Pavel
Functional Polymorphisms in DNA Repair Genes Are Associated with Sporadic Colorectal Cancer Susceptibility and Clinical Outcome.
International Journal of Molecular Sciences. Roč. 20, č. 1 (2019), č. článku 97. E-ISSN 1422-0067
R&D Projects: GA ČR(CZ) GA17-16857S; GA ČR(CZ) GA15-14789S
Institutional support: RVO:68378041
Keywords : DNA repair genes * functional single nucleotide polymorphism * colorectal cancer susceptibility * survival analysis
OECD category: Genetics and heredity (medical genetics to be 3)
Impact factor: 4.556, year: 2019
Method of publishing: Open access
https://www.mdpi.com/1422-0067/20/1/97

DNA repair processes are involved in both the onset and treatment efficacy of colorectal cancer (CRC). A change of a single nucleotide causing an amino acid substitution in the corresponding protein may alter the efficiency of DNA repair, thus modifying the CRC susceptibility and clinical outcome. We performed a candidate gene approach in order to analyze the association of non-synonymous single nucleotide polymorphisms (nsSNPs) in the genes covering the main DNA repair pathways with CRC risk and clinical outcome modifications. Our candidate polymorphisms were selected according to the foremost genomic and functional prediction databases. Sixteen nsSNPs in 12 DNA repair genes were evaluated in cohorts from the Czech Republic and Austria. Apart from the tumor-node-metastasis (TNM) stage, which occurred as the main prognostic factor in all of the performed analyses, we observed several significant associations of different nsSNPs with survival and clinical outcomes in both cohorts. However, only some of the genes (REV3L, POLQ, and NEIL3) were prominently defined as prediction factors in the classification and regression tree analysis, therefore, the study suggests their association for patient survival. In summary, we provide observational and bioinformatics evidence that even subtle alterations in specific proteins of the DNA repair pathways may contribute to CRC susceptibility and clinical outcome.
Permanent Link: http://hdl.handle.net/11104/0299340