Association of genetic predisposition studies in CYP1A1 polymorphism studies in acute myeloid leukemia
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PROVIDER: S-EPMC10821586 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
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Project description:BackgroundEvidence indicates that CYP1A1 MspI polymorphism might be a possible risk factor for several malignancies. A growing body of literature has been devoted to the association of CYP1A1 MspI polymorphism with acute myeloid leukemia (AML). However, the results remain conflicting. The aim of the present study was to derive a more precise estimation of the relationship.MethodsMeta-analyses assessing the association of CYP1A1 MspI variation with AML were conducted and subgroup analyses on ethnicity and age groups were further performed. Eligible studies were identified for the period up to May 2012.ResultsA total of ten case-control studies including 1330 cases and 3688 controls were selected for analysis. The overall data failed to indicate a significant association of CYP1A1 MspI polymorphism with AML risk (C vs T: OR = 1.13; 95%CI = 0.87-1.48; CC vs TT: OR = 1.72; 95%CI = 0.99-3.01; CC + TC vs TT: OR = 1.16; 95%CI = 0.86-1.55). In subgroup analysis stratified by ethnicity, significant AML risk was shown among Asians (CC + TC vs TT: OR = 1.33; 95%CI = 1.09-1.62) but not Caucasians or mixed races. In subgroup analysis regarding age groups, no associations were observed in either the childhood AML or the adult AML subgroups.ConclusionThe results of the present study suggested that CYP1A1 MspI polymorphism might be a risk factor for AML among Asians. Further investigations are needed to confirm the conclusions.
| S-EPMC3444413 | biostudies-literature
Project description:Myelodysplastic syndrome (MDS) is a clonal blood disorder characterized by ineffective hematopoiesis, cytopenias, dysplasia and an increased risk of acute myeloid leukemia (AML). With the growing availability of clinical genetic testing, there is an increasing appreciation that a number of genetic predisposition syndromes may underlie apparent de novo presentations of MDS/AML, particularly in children and young adults. Recent findings of clonal hematopoiesis in acquired aplastic anemia add another facet to our understanding of the mechanisms of MDS/AML predisposition. As more predisposition syndromes are recognized, it is becoming increasingly important for hematologists and oncologists to have familiarity with the common as well as emerging syndromes, and to have a systematic approach to diagnosis and screening of at risk patient populations. Here, we provide a practical algorithm for approaching a patient with a suspected MDS/AML predisposition, and provide an in-depth review of the established and emerging familial MDS/AML syndromes caused by mutations in the ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, SRP72 genes. Finally, we discuss recent data on the role of somatic mutations in malignant transformation in acquired aplastic anemia, and review the practical aspects of MDS/AML management in patients and families with predisposition syndromes.
| S-EPMC4798888 | biostudies-literature
Project description:ObjectiveCytochrome P450 is one of the major drug metabolizing enzyme families and its role in metabolism of cancer drugs cannot be less emphasized. The association be- tween single nucleotide polymorphisms (SNPs) in CYP1A1 and pathogenesis of chronic myeloid leukemia (CML) has been investigated in several studies, but the results observed vary based on varied risk factors. The objective of this study was to investigate the risk factors associated with the CYP1A1*2C [rs1048943: A>G] polymorphism in CML patients and its role in therapeutic response to imatinib mesylate (IM) affecting clinico-pathological parameters, in the Indian population.Materials and methodsIn this case-control study, CYP1A1*2C was analysed in CML patients. After obtaining approval from the Ethics Committee of oncology hospital, we collected blood samples from 132 CML patients and 140 matched controls. Genom- ic DNA was extracted and all the samples were analysed for the presence of the CYP1A1*2C polymorphism using allele-specific polymerase chain reaction, and we examined the relationship of genotypes with risk factors such as gender, age, phase of the disease and other clinical parameters.ResultsWe observed a significant difference in the frequency distribution of CYP1A1*2C genotypes AA (38 vs. 16%, P=0.0001), AG (57 vs. 78%, P=0.0002) and GG (5 vs. 6%, P=0.6635) between patients and controls. In terms of response to IM therapy, significant variation was observed in the frequencies of AA vs AG in major (33 vs 67%) and poor (62 vs 31%) hematological responders, and AA vs AG in major (34 vs. 65%) and poor (78 vs. 22%) cytogenetic responders. However, the patients with the GG homozygous genotype did not show any significant therapeutic outcome.ConclusionThe higher frequency of AG in controls indicates that AG may play a protec- tive role against developing CML. We also found that patients with the AG genotype showed favorable treatment response towards imatinib therapy, indicating that this polymorphism could serve as a good therapeutic marker in predicting response to such therapy.
| S-EPMC4601872 | biostudies-literature
Project description:Although most cases of myeloid neoplasms are sporadic, a small subset has been associated with germline mutations. The 2016 revision of the World Health Organization classification included these cases in a myeloid neoplasm group with a predisposing germline mutational background. These patients must have a different management and their families should get genetic counseling. Cases identification and outline of the major known syndromes characteristics will be discussed in this text.
| S-EPMC5600909 | biostudies-literature
Project description: Not available
| S-EPMC5286952 | biostudies-literature
Project description:Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy. Genome-wide association studies have shown variation at 14q11.2 influences ALL risk. We sought to decipher causal variant(s) at 14q11.2 and the mechanism of tumorigenesis. We show rs2239630 G>A resides in the promoter of the CCAT enhancer-binding protein epsilon (CEBPE) gene. The rs2239630-A risk allele is associated with increased promotor activity and CEBPE expression. Depletion of CEBPE in ALL cells reduces cell growth, correspondingly CEBPE binds to the promoters of electron transport and energy generation genes. RNA-seq in CEBPE depleted cells demonstrates CEBPE regulates the expression of genes involved in B-cell development (IL7R), apoptosis (BCL2), and methotrexate resistance (RASS4L). CEBPE regulated genes significantly overlapped in CEBPE depleted cells, ALL blasts and IGH-CEBPE translocated ALL. This suggests CEBPE regulates a similar set of genes in each, consistent with a common biological mechanism of leukemogenesis for rs2239630 associated and CEBPE translocated ALL. Finally, we map IGH-CEBPE translocation breakpoints in two cases, implicating RAG recombinase activity in their formation.
| S-EPMC6327050 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is a clonal hematopoietic disease that arises from chromosomal and genetic aberrations in myeloid precursor cells. AML is one of the most common types of acute leukemia in adults; however, it is relatively rare overall, comprising about 1% of all cancers. In the last decade or so, numerous genome-wide association studies (GWAS) have been conducted to screen between hundreds of thousands and millions of variants across many human genomes to discover genetic polymorphisms associated with a particular disease or phenotype. In oncology, GWAS has been performed in almost every commonly occurring cancer. Despite the increasing number of studies published regarding other malignancies, there is a paucity of GWAS studies for AML. In this review article, we will summarize the current status of GWAS in AML.
| S-EPMC10377605 | biostudies-literature
Project description:Background and objectiveIsocitrate dehydrogenase genes (IDH1 and IDH2) encode important enzymes that play pivotal role in cellular metabolism. Mutations in TET2 have been demonstrated to contribute to DNA hypermethylation, either expression of mutant IDH1/2 or TET2 resulted in poor cell differentiation and epigenetic alterations in hematopoietic cells, suggesting a sharing of the oncogenetic impact. In this study, we investigated the frequency of genetic alterations in IDH1/2 and TET2 genes in Egyptian cohort of adult patients with de novo AML, and the association of IDH1/2 and TET2 genetic Polymorphism with AML prognostic criteria and explore prognostic molecular markers with clinical outcome.MethodsThe SNP assay for IDH1, IDH2 and TET2 genes polymorphism tested with RT-PCR included three polymorphisms that are rs121913500, rs121913503, and rs2454206 respectively, were tested on 141 adult Egyptian patients fulfilling the AML diagnostic criteria.ResultThe incidence of IDH mutations is 11/141 (7.8%); 5/141 (3.5%) IDH1 mutant and 6/141 (4.3%) IDH2 mutant. And the incidence of TET2 mutations is 72/141 (51.1%); 15/141 (10.7%) homozygous mutation and 57/141 (40.4%) heterozygous mutations. IDH1, IDH2 and TET2 genes mutations with DFS and OS in AML patients were not significantly correlated.ConclusionsTET2 SNP is common in Egyptian AML patients. Further research on IDH, TET2 and their relationships to other hematological malignancies and leukemogenesis transformation is advised and a study of a larger number of cases is needed for potential statistical significance.
| S-EPMC10762743 | biostudies-literature
Project description:Introduction: Historically, the majority of childhood cancers, including acute lymphoblastic leukemia (ALL), were not thought to have a hereditary basis. However, recent germline genomic studies have revealed that at least 5 - 10% of children with cancer (and approximately 3 - 4% of children with ALL) develop the disease due to an underlying genetic predisposition.Areas covered: This review discusses several recently identified ALL predisposing conditions and provides updates on other more well-established syndromes. It also covers topics related to the evaluation and management of children and family members at increased ALL risk.Expert opinion: Germline predisposition is gaining recognition as an important risk factor underlying the development of pediatric ALL. The challenge now lies in how best to capitalize on germline genetic information to improve ALL diagnosis, treatment, and perhaps even prevention.
| S-EPMC10576863 | biostudies-literature
Project description:Objective: To explore the relationship between WT1 rs16754 polymorphism and clinical features and prognosis in patients with acute myeloid leukemia(AML). Methods: Bone marrow samples of 115 newly diagnosed AML patients and peripheral blood samples of 177 healthy controls were collected from the Second Hospital of Shanxi Medical University from January 2010 to December 2013. The genotype of rs16754 was screened by high- resolution melting(HRM)and validated by direct sequencing. The association between the single nucleotide polymorphism(SNP)and the risk, clinical features, remission and survival state of AML patients was analyzed retrospectively. Results: This polymorphism was not associated with risk for AML(P=0.296), the GA/AA group and GG group had no significant difference in gender, age, clinical features and remission rate of chemotherapy(P>0.05), the percentage of bone marrow cells in GA/AA group was higher than that in GG group(P=0.025). The survival state of 99 patients were followed up, single factor analysis found that the difference of the overall survival rate was statistically significant(P=0.035)between the two groups, the rate of GA/AA group was higher than that of the GG group. Multivariate analysis showed that the A allele was an independent prognostic factor for AML patients and the mortality risk of GA/AA patients were higher(HR=1.681, 95% CI 1.046- 2.700, P=0.032). Conclusion: WT1 rs16754 polymorphism is associated with the prognosis of AML, and can be used as one of the indicators for the prognosis of AML patients.
| S-EPMC7364874 | biostudies-literature