DNA Repair Gene Polymorphisms and Their Relation With DNA Damage, DNA Repair, and Total Antioxidant Capacity in Childhood Acute Lymphoblastic Leukemia Survivors

Dinçer, Yıldız; Yüksel, Selin; Batar, Bahadır; Güven, Mehmet; Onaran, İlhan; Çelkan, Tiraje

doi:10.1097/mph.0000000000000133

Cited by 12 publications

(10 citation statements)

References 33 publications

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“…Some studies have reported a strong association between the XPD Lys751Gln polymorphism and increased leukemia risk, 20 , 21 , 39 while one study found decreased risk of the leukemia. 26 In the current study, XPD Lys751Gln polymorphism was found to be associated with increased risk for CML. These results are in agreement with Bănescu et al 39 To examine the effect of gene–gene interactions as an estimation for CML risk in the present study, the relationship between dual gene–gene combinations was also analyzed.…”

Section: Discussionmentioning

confidence: 49%

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Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia

Abdalhabib¹,

Jackson²,

Alzahrani³

et al. 2021

PGPM

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Purpose Glutathione S -transferases (GSTT1 and GSTM1) are instrumental in detoxification process of activated carcinogens. Nucleotide excision repair is carried out by DNA helicase encoded by xeroderma pigmentosum group D (XPD) genes and aberrations in the XPD gene predisposes to increased risk of cancer. The present study aimed to investigate GSTT1, GSTM1 and XPD polymorphisms in newly diagnosed chronic myeloid leukemia (CML) patients and to examine the association of these polymorphisms with the risk of developing CML. Patients and Methods This case–control study was carried out from June 2019 to August 2021 involving 150 newly diagnosed patients with CML and an equal number of randomly selected age- and sex-matched healthy individuals. A multiplex-PCR assay was used to genotype GSTT1 null and GSTM1 null polymorphisms. XPD gene polymorphism was detected by PCR-RFLP using predesigned gene-specific primers. Results GSTT1 and GSTM1 null polymorphisms were detected in 42.7% and 61.3% of cases, respectively, compared to 18% and 35.3% for controls. The combination of both GST null polymorphisms revealed a significant association with CML. Frequencies of XPD Lys751Gln genotypes in cases were 62.7% heterozygous Lys/Gln, 24% homozygous Lys/Lys and 13.3% homozygous Gln/Gln, while in the controls were 74.7%, 20%, and 5.3%, respectively. Significant differences were also noted regarding the combination of GSTT1/GSTM1 null with XPD Lys/Lys, and GSTM1 null with XPD Lys/Lys. Conclusion In conclusion, GSTT1 null, GSTM1 null and XPD polymorphisms showed positive association with the risk of development of CML. Furthermore, age and gender did not exhibit any association with the studied polymorphisms, while CML phases were associated with GSTT1 null polymorphism.

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Section: Discussionmentioning

confidence: 49%

“… 25 Nucleotide excision repair and basal transcription are carried out by helicase encoded by XPD genes and aberrations in the XPD gene predisposes to increased risk of cancer. 26 …”

Section: Discussionmentioning

confidence: 99%

Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia

Abdalhabib¹,

Jackson²,

Alzahrani³

et al. 2021

PGPM

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“…The clinical biochemical indices of patients with ALL showed a marked increase in the levels of malondialdehyde, an important biochemical index for plasma oxidative stress [ 70 ], and a notable increase in the levels of 8-oxodG and 8-OHdG, biomarkers of oxidative DNA damage in urine, in patients with ALL [ 71 , 72 ]. In addition, the level of oxidatively modified DNA bases in lymphocytes from children with ALL was markedly higher than that in children without the disease [ 73 , 74 , 75 ]. Abundant evidence has shown that ROS have a vital role in secondary gene events in ALL.…”

Section: The Role Of Redox Dyshomeostasis In the Occurrence Of Allmentioning

confidence: 99%

Redox Control in Acute Lymphoblastic Leukemia: From Physiology to Pathology and Therapeutic Opportunities

Chen

Zhao

2021

Cells

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Acute lymphoblastic leukemia (ALL) is a hematological malignancy originating from B- or T-lymphoid progenitor cells. Recent studies have shown that redox dysregulation caused by overproduction of reactive oxygen species (ROS) has an important role in the development and progression of leukemia. The application of pro-oxidant therapy, which targets redox dysregulation, has achieved satisfactory results in alleviating the conditions of and improving the survival rate for patients with ALL. However, drug resistance and side effects are two major challenges that must be addressed in pro-oxidant therapy. Oxidative stress can activate a variety of antioxidant mechanisms to help leukemia cells escape the damage caused by pro-oxidant drugs and develop drug resistance. Hematopoietic stem cells (HSCs) are extremely sensitive to oxidative stress due to their low levels of differentiation, and the use of pro-oxidant drugs inevitably causes damage to HSCs and may even cause severe bone marrow suppression. In this article, we reviewed research progress regarding the generation and regulation of ROS in normal HSCs and ALL cells as well as the impact of ROS on the biological behavior and fate of cells. An in-depth understanding of the regulatory mechanisms of redox homeostasis in normal and malignant HSCs is conducive to the formulation of rational targeted treatment plans to effectively reduce oxidative damage to normal HSCs while eradicating ALL cells.

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“…Increased TOS values in other types of cancer such as thyroid and colorectal cancers were also observed [ 24 , 25 ]. During anticancer therapy, a decrease of TAC was found, but in cancer survivors, this parameter was not different from that in the control group [ 26 , 27 ]. In pediatric patients with tumors, including osteosarcoma and Ewing’s sarcoma, various levels of the GSH/GSSG ratio in serum were obtained before treatment [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Oxidative and Antioxidative Status Expressed as OSI Index and GSH/GSSG Ratio in Children with Bone Tumors after Anticancer Therapy Completion

Gajewska¹,

Chełchowska²,

Rychłowska-Pruszyńska³

et al. 2022

JCM

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Aims. There are no data on the redox status of children with bone tumors in complete disease remission. Therefore, the presented study examined the reduced/oxidized glutathione (GSH/GSSG) ratio, total oxidant capacity (TOC) and total antioxidant capacity (TAC) values as well as the oxidative stress index (OSI) for assessing alterations in the oxidant/antioxidant balance in 35 children with osteosarcoma or Ewing’s sarcoma after anticancer therapy completion (median 14 months) compared with a control group. Methods. GSH, GSSG, TOC, TAC concentrations and bone alkaline phosphatase (BALP) activity were evaluated by immunoenzymatic (ELISA) and enzymatic methods. Results. We found no differences in serum BALP activity between all survivors with bone tumors and the control group. Patients with osteosarcoma after anticancer therapy completion had significantly higher values of TAC, GSH and the GSH/GSSG ratio as well as GSSG than healthy subjects. In patients with Ewing’s sarcoma, we found significantly higher values of TOC concentration compared with healthy children. In addition, survivors with Ewing’s sarcoma had higher TOC concentrations and OSI index values (p < 0.01), but a lower GSH/GSSG ratio (p < 0.05) than survivors with osteosarcoma. A positive correlation between TOC and the post-therapy period was observed in survivors. Conclusions. We found that in survivors with bone tumors, a disturbed balance between prooxidants and antioxidants persists after the completion of anticancer treatment. Moreover, an increased TOC value together with the post-therapy period may suggest increasing oxidative processes in survivors with bone tumors after treatment. Further observations will allow assessment of the relationship between the oxidant/antioxidant status and the predisposition of survivors to bone neoplastic disease recurrence.

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DNA Repair Gene Polymorphisms and Their Relation With DNA Damage, DNA Repair, and Total Antioxidant Capacity in Childhood Acute Lymphoblastic Leukemia Survivors

Cited by 12 publications

References 33 publications

Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia

Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia

Redox Control in Acute Lymphoblastic Leukemia: From Physiology to Pathology and Therapeutic Opportunities

Oxidative and Antioxidative Status Expressed as OSI Index and GSH/GSSG Ratio in Children with Bone Tumors after Anticancer Therapy Completion

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