Dataset Information

Polymorphism of XRCC1, XRCC3, and XPD genes and risk of chronic myeloid leukemia.

ABSTRACT: The genetic polymorphisms of X-ray repair cross complementing group 1 (XRCC1), X-ray repair cross complementing group 3 (XRCC3), and xeroderma pigmentosum complementation group D (XPD) repair genes may lead to genetic instability and leukemogenesis. The purpose of the study was to evaluate the association between XRCC1 Arg399Gln, Arg280His and Arg194Trp, XRCC3 Thr241Met, and XPD Lys751Gln polymorphisms and the risk of developing CML in Romanian patients. A total of 156 patients diagnosed with CML and 180 healthy controls were included in this study. We found no association between CML and XRCC1 or XRCC3 variant genotypes in any of the investigated cases. A significant difference was observed in the variant genotype frequencies of the XPD Lys751Gln polymorphism between the patients with CML and control group (for variant homozygous genotypes, OR = 2.37; 95% CI = 1.20-4.67; P value = 0.016 and for combined heterozygous and variant homozygous genotypes, OR = 1.72; 95% CI = 1.10-2.69; P value = 0.019). This was also observed when analyzing the variant 751Gln allele (OR = 1.54; 95% CI = 1.13-2.11; P value = 0.008). Our results suggest that the XPD Lys751Gln variant genotype increases the risk of CML.

SUBMITTER: Banescu C

PROVIDER: S-EPMC4052066 | biostudies-other | 2014

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Polymorphism of XRCC1, XRCC3, and XPD genes and risk of chronic myeloid leukemia.

Bănescu Claudia C Trifa Adrian P AP Demian Smaranda S Benedek Lazar Erzsebeth E Dima Delia D Duicu Carmen C Dobreanu Minodora M

BioMed research international 20140515

The genetic polymorphisms of X-ray repair cross complementing group 1 (XRCC1), X-ray repair cross complementing group 3 (XRCC3), and xeroderma pigmentosum complementation group D (XPD) repair genes may lead to genetic instability and leukemogenesis. The purpose of the study was to evaluate the association between XRCC1 Arg399Gln, Arg280His and Arg194Trp, XRCC3 Thr241Met, and XPD Lys751Gln polymorphisms and the risk of developing CML in Romanian patients. A total of 156 patients diagnosed with CM ...[more]

PMID: 24955348

Similar Datasets

Project description:BackgroundChronic myeloid leukemia (CML) is a myeloproliferative neoplasm where pathogenesis is based on the oncoprotein termed BCR-ABL1.1 TET2 initiates DNA demethylation and is frequently mutated in hematological malignancies, including CML. The relation between TET2 acquisition and CML transformation and/or imatinib resistance is needed to be investigated.2.AimTo evaluate Ten Eleven Translocation 2 gene (TET2) single nucleotide polymorphism (SNP) (rs2454206, rs34402524, rs61744960) in chronic myeloid leukemia (CML) in relation to the disease prognostic criteria.Materials & methodThe study included 84 subjects; 54 CML in chronic phase and 30 healthy subjects as control group matched for age and sex. Routine investigations, including CBC, bone marrow aspiration, biochemical investigations, and molecular study, were performed in CML patients to identify the disease stage. DNA extraction and SNP assay for TET2 gene polymorphism were done using (Thermo-Fisher predesigned SNP, USA) PCR prism 7500.ResultsThe mean age was 45.98±15.7 yrs in CML patients and 39.3±6.587 yrs in the control group (p>0.05). TET2 SNP rs 34402524 was either heterozygous or homozygous in CML (48%, 46.2% respectively) but was mainly homozygous among control (80%) group (p=0.012). TET2 SNP rs 2454206 wild type within CML was detected in 65.4% of patients and in controls was 63.3% (p=0.046). TET2 SNP rs 61744960 showed a homozygous pattern among all groups (CML and control) (p=0.528). TET2 SNP in CML cases did not alter the prognostic criteria as no statistical significance was noted (p>0.05) yet, it was significantly related to spleen size in rs 34402524 where the homozygous group had larger spleen size and higher BCR-ABL1 levels six months after starting TKIs (p<0.05).Conclusions/recommendationTET2 SNP is common among Egyptian chronic myeloid leukemia. TET2 SNP rs 3442524 was associated with larger spleen size and higher BCR-ABL1 levels after six months of starting TKIs suggesting disease progression.

Project description:The first treatment of chronic myeloid leukemia (CML) included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT) marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients were cured. The second breakthrough was the introduction of human recombinant interferon-alfa, able to achieve a complete cytogenetic remission in 15% to 30% of patients, with a significant survival advantage over conventional chemotherapy. At the end of the last century, about 15 years ago, all these treatments were quickly replaced by a class of small molecules targeting the tyrosine kinases (TK), which were able to induce a major molecular remission in most of the patients, without remarkable side effects, and a very prolonged life-span. The first approved TK inhibitor (TKI) was Imatinib Mesylate (Glivec or Gleevec, Novartis). Rapidly, other TKIs were developed tested and commercialized, namely Dasatinib (Sprycel, Bristol-Myers Squibb), Nilotinib (Tasigna, Novartis), Bosutinib (Busulif, Pfizer) and Ponatinib (Iclusig, Ariad). Not all these compounds are available worldwide; some of them are approved only for second line treatment, and the high prices are a problem that can limit their use. A frequent update of treatment recommendations is necessary. The current treatment goals include not only the prevention of the transformation to the advanced phases and the prolongation of survival, but also a length of survival and of a quality of life comparable to that of non-leukemic individuals. In some patient the next ambitious step is to move towards a treatment-free remission. The CML therapy, the role of alloSCT and the promising experimental strategies are reviewed in the context of the new therapeutic goals.

Project description:A previous study has demonstrated a significant decrease in the TCR? gene expression level in chronic myeloid leukemia (CML); thus, we further investigated the expression of TCR?-regulating factors, the distribution of the TCR? 3' untranslated region (3'-UTR) splice variants, and the expression level and correlation of the alternative splicing factor/splicing factor 2 (ASF/SF-2), Fc?RI? and ZAP-70 genes. TCR? 3'-UTR splice variants were identified in peripheral blood mononuclear cells (PBMCs) from 14 healthy individuals, 40 patients with CML and 22 patients with CML in complete remission (CML-CR) by RT-PCR. The expression level of the TCR?, Fc?RI?, ASF/SF-2 and ZAP-70 genes was analyzed by real-time quantitative PCR. While the expression of TCR? gene in the CML group was significantly lower than that in the healthy individual and CML-CR groups, a significantly higher expression of the FceRI? and ASF/SF-2 genes was found in the CML group. Two types of splicing forms were detected in all of the healthy individual CML-CR cases: wild type (WT) TCR? 3'-UTR and alternatively splieced (AS) TCR? 3'-UTR which have been alternatively splieced in the WT TCR? 3'-UTR . However, 35% of the CML cases contained only the wild type TCR? 3'-UTR isoform. Based on the TCR? 3'-UTR isoform expression characteristic, we divided the patients with CML into two subgroups: the WT+AS- CML group, containing patients that express only the wild type TCR? 3'-UTR, and the WT+AS+ CML group, which contained patients that expressed two TCR? 3'-UTR isoforms. A significantly different ASF/SF-2 and Fc?RI? gene expression pattern was found between the WT+AS- and WT+AS+CML groups. We concluded that defective TCR? expression may be characterized in the WT+AS-and WT+AS+CML subgroups by the different gene expression pattern. The overexpression of ASF/SF2, which alternatively splices the TCR? 3'-UTR, is thought to participate in feedback regulation. The characteristics of TCR? 3'-UTR alternative splicing may be a novel immunological marker for the evaluation of the CML immune status.

Dataset Information

Polymorphism of XRCC1, XRCC3, and XPD genes and risk of chronic myeloid leukemia.

Publications

Polymorphism of XRCC1, XRCC3, and XPD genes and risk of chronic myeloid leukemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets