Polymorphisms of DNA repair genes are related to the pathogenesis of myelodysplastic syndrome

Some studies show that alterations in DNA repair genes polymorphisms are associated with the pathogenesis and susceptibility of Myelodysplastic Syndrome (MDS). We genotyped 60 MDS patients for six DNA repair gene polymorphisms: BRCA1 rs4793191, BRCA2 rs9567623, RAD51 rs1801320, XRCC5 rs3835, XRCC6 rs2267437 and LIG4 rs1805388. The G/C heterozygote genotype of rs1801320 polymorphism was associated with a decreased chance of developing MDS (p = 0.05). Additionally, the G/G homozygous genotype was associated with the presence of one cytopenia in whole blood. The genotype C/G and CG + GG of the rs2267437 polymorphism was associated with normal karyotype (p = 0.010) and bone marrow cellularity normocellular + hypercellular (p = 0.023). We found that the A/G heterozygous genotype of the rs3835 polymorphism is associated with decreased chance of developing MDS (p < 0.001). These results support the importance of RAD51, XRCC5 and XRCC6 genes polymorphisms in the maintenance of genomic stability promoting a better understanding of the genesis and etiology of MDS. Copyright © 2014 John Wiley & Sons, Ltd.

[1]  L. Marks,et al.  Lung , 2013, ALERT • Adverse Late Effects of Cancer Treatment.

[2]  R. Pinheiro,et al.  Beyond race-related disparities: is myelodysplastic syndrome the same everywhere? , 2013, Leukemia & lymphoma.

[3]  R. Pinheiro,et al.  ATM polymorphism is associated with low risk myelodysplastic syndrome. , 2013, DNA repair.

[4]  D. Mikulenková,et al.  DNA repair gene variants are associated with an increased risk of myelodysplastic syndromes in a Czech population , 2013, Journal of Hematology & Oncology.

[5]  F. Naeim.  8 – Myelodysplastic Syndromes/Neoplasms—Overview , 2013 .

[6]  A. Raza,et al.  The genetic basis of phenotypic heterogeneity in myelodysplastic syndromes , 2012, Nature Reviews Cancer.

[7]  M. Cazzola,et al.  Classification and prognostic evaluation of myelodysplastic syndromes. , 2011, Seminars in oncology.

[8]  Lin Li,et al.  Detoxification and DNA repair genes polymorphisms and susceptibility of primary myelodysplastic syndromes in Chinese population. , 2011, Leukemia research.

[9]  S. de Vos,et al.  Identification of defects in the transcriptional program during lineage-specific in vitro differentiation of CD34(+) cells selected from patients with both low- and high-risk myelodysplastic syndrome. , 2010, Experimental hematology.

[10]  Yan Song,et al.  Interaction between BRCA1/BRCA2 and ATM/ATR associate with breast cancer susceptibility in a Chinese Han population. , 2010, Cancer genetics and cytogenetics.

[11]  M. Sekeres.  The epidemiology of myelodysplastic syndromes. , 2010, Hematology/oncology clinics of North America.

[12]  D. Berry,et al.  DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  T. Economopoulos,et al.  Expression analysis of proteins involved in the non homologous end joining DNA repair mechanism, in the bone marrow of adult de novo myelodysplastic syndromes , 2010, Annals of Hematology.

[14]  R. Pinheiro,et al.  Comparison of I-FISH and G-banding for the detection of chromosomal abnormalities during the evolution of myelodysplastic syndrome. , 2009, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[15]  K. Hopfner.  DNA Double-Strand Breaks Come into Focus , 2009, Cell.

[16]  M. Voso,et al.  Polymorphisms of detoxification and DNA repair enzymes in myelodyplastic syndromes. , 2009, Leukemia research.

[17]  H. Hsu,et al.  Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end‐joining pathway genes , 2009, Cancer.

[18]  M. Jädersten,et al.  Myelodysplastic syndromes: biology and treatment , 2009, Journal of internal medicine.

[19]  D. Steensma,et al.  RAD51 and XRCC3 polymorphism frequency and risk of myelodysplastic syndromes , 2008, American journal of hematology.

[20]  Zhengdong Zhang,et al.  Genetic variants of the XRCC7 gene involved in DNA repair and risk of human bladder cancer , 2008, International journal of urology : official journal of the Japanese Urological Association.

[21]  R. Baan,et al.  Genetic polymorphisms and micronucleus formation: a review of the literature. , 2008, Mutation research.

[22]  M. Lieber,et al.  The Mechanism of Human Nonhomologous DNA End Joining* , 2008, Journal of Biological Chemistry.

[23]  T. Helleday,et al.  DNA double-strand break repair: from mechanistic understanding to cancer treatment. , 2007, DNA repair.

[24]  M. Silva,et al.  FLT3 mutation and AML/ETO in a case of Myelodysplastic syndrome in transformation corroborates the two hit model of leukemogenesis. , 2007, Leukemia research.

[25]  B. Friedenson,et al.  The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers , 2007, BMC Cancer.

[26]  F. Sassi,et al.  Lymphatic vessels assessment in feline mammary tumours , 2007, BMC Cancer.

[27]  L. Larocca,et al.  Reduced BRCA1 expression due to promoter hypermethylation in therapy-related acute myeloid leukaemia , 2006, British Journal of Cancer.

[28]  David J. Chen,et al.  Role of non-homologous end joining (NHEJ) in maintaining genomic integrity. , 2006, DNA repair.

[29]  Jeremy M. Stark,et al.  Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability , 2004, Oncogene.

[30]  Chen-Yang Shen,et al.  Breast cancer risk associated with genotypic polymorphism of the nonhomologous end-joining genes: a multigenic study on cancer susceptibility. , 2003, Cancer research.

[31]  P. Sung,et al.  Homologous DNA Pairing by Human Recombination Factors Rad51 and Rad54* , 2002, The Journal of Biological Chemistry.

[32]  D. Durocher,et al.  DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme? , 2001, Current opinion in cell biology.

[33]  Thomas Ried,et al.  DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation , 2000, Nature.

[34]  P. Jeggo,et al.  Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient , 1999, Current Biology.

[35]  T Hamblin,et al.  International scoring system for evaluating prognosis in myelodysplastic syndromes. , 1997, Blood.