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• W2339947034 abstract "Abstract Background Base excision repair (BER) is critical for genome maintenance, and is mainly responsible for the correction of small base changes of DNA damage. BER pathway involved many enzymes including OGG1, XRCC1, APE1 and MUTYH. Single nucleotide polymorphisms (SNPs) in DNA repair genes result reduced DNA repair capacity, have been reported to be associated with an increased risk of various cancers including hematologic malignancies. However, it is unclear that these polymorphisms alter the susceptibility and clinical outcome of myelodysplastic syndromes (MDS) patients. The aim of this study is to evaluate the association of polymorphisms in gene encoding four key proteins of DNA BER: OGG1 Ser326Cys, XRCC1 Arg399Gln, APE1 Asp148Glu, and MUTYHGln324His with the susceptibility and clinical features of MDS. Methods Our study included 113 MDS patients [median 68.3 years, range 17.1-86.5 years; male/female 76/37; RCUD (n=37), RARS (n=6), RCMD (n=21), MDS-u (n=11), RAEB-1(n=14), RAEB-2 (n=11), others (n=13)] and 192-health control group. Twenty four patients with MDS had the history of cancer. Genetic polymorphisms in BER pathway genes were examined using PCR and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotype and allele frequencies were compared between patients group and control group by using χ2-test. All patients and healthy controls received written information about the study. This study was approved by the International Research Board of Gunma University Hospital. Results There was no statistically significant difference in the allele and genotype frequencies of the OGG1 Ser326Cys, XRCC1 Arg399Gln, APE1 Asp148Glu, and MUTYH Gln324His polymorphisms between the MDS patients and the control group. In the analysis of clinical characteristics, XRCC1 non Arg/Arg genotype (low DNA repair type) was significantly associated with lower Hb level (8.64±2.29g/dL vs. 9.96±2.08 g/dL, p<0.005) and higher frequency of the complex karyotype (14.9% vs. 2.8%, p=0.05). Furthermore, XRCC1 non Arg/Arg genotype was associated with therapy- related MDS (OR 3.15, 95% CI 1.24-7.98, p=0.02) and especially the past history of radiotherapy (14.3% vs. 0%, p<0.005). In contrast, the polymorphisms in OGG1 Ser326Cys, APE1 Asp148Glu, and MUTYH Gln324His were not involved in the clinical features of MDS. Conclusion The low DNA repair polymorphism, XRCC1 Arg399Gln is associated with the clinical features of MDS, including therapy- related MDS. Further investigation of BER polymorphisms will provide the understanding of pathogenesis of therapy- related MDS in a larger sample size analysis. Disclosures: No relevant conflicts of interest to declare." @default.
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• W2339947034 date "2013-11-15" @default.
• W2339947034 modified "2023-09-30" @default.
• W2339947034 title "The Polymorphism Of Base Excision Repair Gene, XRCC1 Arg399Gln Is Associated With The Therapy-Related Myelodysplastic Syndromes (MDS)" @default.
• W2339947034 doi "https://doi.org/10.1182/blood.v122.21.4085.4085" @default.
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