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Susceptibility to MDS: DNA Repai r and Detoxification Genes

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The Myelodysplastic Syndromes

Abstract

There are many environmental and genetic factors that are likely to predispose an individual to myelodysplastic syndrome (MDS). Factors influencing the level of DNA damage within a cell are particularly important in conferring disease susceptibility because, if expressed, DNA damage may result in genetic alterations and if these occur in haematopoietic stem cells (HSCs) a clonal disease can arise. Cells harbour detoxification systems which act to minimise the risk of damaging agents reaching the DNA or, if DNA damage occurs, complex repair systems exist to rid the genome of the damage. The bone marrow is at high risk from genotoxic agents and differences in how an individual detoxifies, and repairs damage from, harmful agents are important contributory factors in the development of bone marrow diseases including MDS. A large number of the genes involved in the detoxification and repair processes are polymorphic and may therefore contribute to inter-individual variability in the capacity to manage DNA damage. This chapter reviews our current knowledge of detoxification and DNA repair gene variants in MDS and whether they confer susceptibility to the disease.

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Acknowledgements

The authors are very grateful to the Nottinghamshire Leukaemia Appeal and the James Skillington Challenge for funding for their research.

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  1. Department of Academic Haematology, University of Nottingham, Clinical Sciences Building, Nottingham University Hospitals—City Campus, NG5 1PB, Nottingham, UK

    Claire Seedhouse & Nigel Russell

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Correspondence to Claire Seedhouse .

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  1. , 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, Budapest, 1125, Hungary

    Judit Várkonyi

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Seedhouse, C., Russell, N. (2011). Susceptibility to MDS: DNA Repai r and Detoxification Genes. In: Várkonyi, J. (eds) The Myelodysplastic Syndromes. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0440-4_2

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