What's Your Poison? Impact of Individual Repair Capacity on the Outcomes of Genotoxic Therapies in Cancer. Part I—Role of Individual Repair Capacity in the Constitution of Risk for Late-Onset Multifactorial Disease

Individual capacity for DNA repair and maintenance of genomic integrity: a fertile ground for studies in the field of assisted reproduction

“…The genotypeÀphenotype correlations of the capacity to maintain genomic integrity have only begun to reveal their potential for use in biomedical applications. Several genetic polymorphisms in genes coding for proteins responsible for repair of DNA damage and maintenance of genomic integrity that may modulate the chances of successful conception and carrying pregnancy to term have already been identified (reviewed in [39,40]). These polymorphisms are generally common (some of them, such as the TP53 Pro72Arg polymorphism, may be very common).…”

The success of stem cell transplantations and the potential post-transplantation complications may be dependent, among other factors, on the capacity of the recipient and the transplanted cells to repair DNA damage

“…Nevertheless, under conditions where the main checkpoints for presence of DNA damage are virtually nonexistent for the duration of many cell divisions, the risk for introduction of alterations in the sequence and structure of DNA may become significant, especially in cell lines that are characterised by inherently low capacity for identification and repair of DNA damage. Carriership of some of the common polymorphisms in genes coding for proteins of DNA repair and maintenance of genome integrity are known to be associated with increased genomic instability in cultured cells -namely, the already mentioned polymorphisms XPC Lys939Gln, XPD Lys751Gln, XRCC3 Thr241 Met and others such as XPG (ERCC5) Asp1104His (rs17655) and XRCC1 Arg399Gln (rs25487) (Vodicka et al 2004, Petkova et al 2013. These, and potentially other polymorphisms in genes coding for products functioning in repair by homologous recombination such as XRCC2 and NBS1, may have specific significance in pluripotent cells relying primarily on homologous recombination to maintain their genome in optimal condition.…”

“…This was only the beginning of the studies on the role of IRC in human health and disease. It had later become clear that the capacity for DNA repair and management of genomic integrity in humans could have significant effects on the risk for development of many common diseases with late onset, such as diabetes and cancer (Roy et al 2007, Petkova et al 2011b, Schiewer and Knudsen 2016, cardiovascular disease (Chelenkova et al 2014, Wu andRoks 2014), neurodegenerative disease (Coppedè and Migliore 2015, Nayyar et al 2015); and that it could potentially reflect on the susceptibility for disease in different individuals, and at different ages (Cherdyntseva et al 2010, Petkova et al 2013 and the outcomes of different genotoxic treatments (Kan and Zhang 2015, Velic et al 2015, Petkova et al 2014b. DNA damage repair pathways began to be regarded as useful therapeutic targets in cancer therapy, , Khalil et al 2012b, Khalil et al 2012c, Gavande et al 2016.…”

Some problems and errors in cytogenetic biodosimetry

“…Nevertheless, agents and/or treatments that produce rapid and severe suppression of cell division are inevitably associated with increased rates of adverse effects (anaemia, agranulocytopenia, mucositis, epilation, etc.). Carriership of polymorphisms in genes coding for proteins of DNA damage-associated response and/or DNA repair may be associated with differential response to radiotherapy in terms of survival and/or rates of adverse effects [19,20]. Low levels of mRNA of proteins acting in replicative synthesis of DNA (ERCC1, RRM1) and heterozygous carriership of the single-nucleotide polymorphism ERCC1 T19007C may be associated with increased chances for tumour regression/increased survival in patients with certain types of solid tumours treated with radiotherapy alone or as part of a combined chemotherapy/radiotherapy regimen [21][22][23][24].…”