Influence of genetic polymorphisms of xenobiotic metabolizing enzymes on the risk of developing leukemia in a Tunisian population

Ouerhani, Slah; Nefzi, Mohamed Ali; Menif, Samia; Safra, Ines; Douzi, Kais; Fouzai, Chaker; Ghorbel, Ghofrane Ben; Bahria, Islem Ben; Elgaaied, Amel Ben Ammar; Abbès, Salem

doi:10.1684/bdc.2011.1502

Cited by 14 publications

(13 citation statements)

References 31 publications

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“…Several genes represented in these methylation clusters have shown to be of relevance to AML and included: GSTM1 for which a methylation probe-set cg18938907 (GSTM1) had the 5th strongest evidence for bimodal methylation levels and showed markedly less methylation in subgroups A, C, E than in other subgroups, GSTM1/GSTT1 deletions been implicated in AML and might be a contributor to the observed bimodal distribution [ 28 , 29 ]. HOXA5 probe-set cg02916332 was hypermethylated in subgroup C, consistent with the previous reports showing it to be differentially methylated and expressed across molecular subgroups of AML [ 30 , 31 ].…”

Section: Resultsmentioning

confidence: 99%

DNA Methylation Clusters and Their Relation to Cytogenetic Features in Pediatric AML

Lamba

Cao

Raimondi

et al. 2020

Cancers

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Acute Myeloid Leukemia (AML) is characterized by recurrent genetic and cytogenetic lesions that are utilized for risk stratification and for making treatment decisions. In recent years, methylation dysregulation has been extensively studied and associated with risk groups and prognosis in adult AML, however, such studies in pediatric AML are limited. Moreover, the mutations in epigenetic genes such as DNMT3A, IDH1 or IDH2 are almost absent or rare in pediatric patients as compared to their abundance in adult AML. In the current study, we evaluated methylation patterns that occur with or independent of the well-defined cytogenetic features in pediatric AML patients enrolled on multi-site AML02 clinical trial (NCT00136084). Our results demonstrate that unlike adult AML, cytosine DNA methylation does not result in significant unique clusters in pediatric AML, however, DNA methylation signatures correlated significantly with the most common and recurrent cytogenetic features. Paired evaluation of DNA methylation and expression identified genes and pathways of biological relevance that hold promise for novel therapeutic strategies. Our results further demonstrate that epigenetic signatures occur complimentary to the well-established chromosomal/mutational landscape, implying that dysregulation of oncogenes or tumor suppressors might be leveraging both genetic and epigenetic mechanisms to impact biological pathways critical for leukemogenesis.

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Section: Resultsmentioning

confidence: 99%

DNA Methylation Clusters and Their Relation to Cytogenetic Features in Pediatric AML

Lamba

Cao

Raimondi

et al. 2020

Cancers

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“…After screening the full articles, a total of 12 studies published between 1999 and 2015 were included in the final meta-analyses. [3,15,21–25,33–37]…”

Section: Resultsmentioning

confidence: 99%

“…Study quality was assessed by NOS, and the scores ranged from 6 to 8, so the studies were considered to be high quality (Table 1). Apart from this, 8 studies with 12 datasets involving 1522 AL patients and 2688 controls of the rapid and slow acetylators phenotypes were included to assess the association between NAT2 phenotypes and AL risk [15,21–23,25,34,36,37] and study quality was also assessed by NOS, and the scores ranged from 6 to 8, which are summarized in Table 2.…”

Section: Resultsmentioning

confidence: 99%

Association between NAT2 polymorphisms and acute leukemia risk

et al. 2019

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“…Several studies have attempted to explain the association between NAT2 polymorphism and numerous cancer types including breast, lung cancer, acute lymphoblastic leukemia and acute myeloid leukemia (Liu et al, 2015;Zou et al, 2017;Hara et al, 2017). However, there are only a limited number of published studies on its association with CML (Ouerhani et al, 2011;Lemos et al, 1999), and this study focuses on the impact of NAT2 (C481T (rs1799929), G590A (rs1799930), A803G (rs1208) and G857A (rs1799931) polymorphisms on the disease (Santos et al, 2016).…”

Section: Evaluation Of Genetic Polymorphisms Of N-acetyltransferase 2mentioning

confidence: 99%

Evaluation of Genetic Polymorphisms of N-acetyltransferase 2 and Relation with Chronic Myeloid Leukemia

Tebien

Khalil

Mills

et al. 2020

Asian Pac J Cancer Prev

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Objectives: The N-Acetyltransferase 2 (NAT2) gene encodes a key enzyme involved in xenobiotic metabolism, which contributes to the detoxification of numerous cancer therapy-induced products. However, the NAT2 genotype/phenotype is not fully understood and few studies have reported its relationship with CML. The aim of this study was to determine whether its polymorphisms ( C481T, G590A, 803A>G and 857G>A ) have a role in chronic myeloid leukemia susceptibility (CML) in Sudanese population. Methods: We performed a case- control study. DNA from 200 CML patients and 100 controls was analyzed for the NAT2 polymorphisms using PCR-RFLP assay. Results: The study showed NAT2 polymorphisms 803AG are associated with CML protection by a factor of 2.3, (OR = 0.044, 95% CI: 0.020-0.095, p = 0. 000). The study indicated that the heterozygous (GA) and mutant (AA) variants of the G857A genotype also offer protection, (OR = 0.002, 95% CI: 0.002-0.019, p = 0. 000) and (OR = 0.018, 95% CI: 0.002-0.133, p = 0. 000), respectively. Conclusion: There was no significant difference in CML diagnosis among Sudanese cases with the 481C→T and 590G→A polymorphisms. But patients with the compound NAT2 genotypes 481CT/803 AG, 590AG/ 803AG, 590AG/ 803GG, 590AA/ 803AG and 590GG/ 803AG were found to have a reduced risk. The current study demonstrates that polymorphisms of NAT2 A803G and G857A might also act as protective factors against developing the disease.

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Influence of genetic polymorphisms of xenobiotic metabolizing enzymes on the risk of developing leukemia in a Tunisian population

Cited by 14 publications

References 31 publications

DNA Methylation Clusters and Their Relation to Cytogenetic Features in Pediatric AML

DNA Methylation Clusters and Their Relation to Cytogenetic Features in Pediatric AML

Association between NAT2 polymorphisms and acute leukemia risk

Evaluation of Genetic Polymorphisms of N-acetyltransferase 2 and Relation with Chronic Myeloid Leukemia

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