C677T and A1298C polymorphisms of methylene tetrahydrofolate reductase in non-Hodgkin lymphoma: southeast Iran

Mashhadi, Mohammad Ali; Miri‐Moghaddam, Ebrahim; Arbabi, Narges; Bazi, Ali; Heidari, Zahra; Sepehri, Zahra; Karimkoshte, Azra; Rezvan, Alireza; Hashemi, Seyed Mehdi

doi:10.5301/tj.5000634

Cited by 6 publications

(11 citation statements)

References 33 publications

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“…33 In our series, this combination was present in patients having non-Hodgkin lymphoma and this finding would deserve to be further investigated. 34…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms C677T and A1298C of MTHFR Gene: Homocysteine Levels and Prothrombotic Biomarkers in Coronary and Pulmonary Thromboembolic Disease

Lupi‐Herrera

Soto

Lugo-Dimas

et al. 2018

Clin Appl Thromb Hemost

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The activity of the enzyme methylenetetrahydrofolate reductase (MTHFR) determines homocysteine (Hcy) levels, and polymorphisms in its gene affect the activity of the enzyme. Changes in the enzyme's activity may lead to a higher susceptibility to develop arterial and venous thromboembolic disease. The aim was to analyze the relationship between the C677T and A1298C polymorphisms of MTHFR, Hcy levels, and prothrombotic biomarkers in pulmonary embolism (PE) and acute myocardial ischemia (AMI). Clinical files of patients with thromboembolic diseases having complete data and whose doctor had requested an assay to determine the polymorphisms of the MTHFR gene, Hcy levels, and prothrombotic biomarkers were studied to search for the correlation between mutations of the MTHFR gene and Hcy levels in the different diseases. We included 334 files: 158 were from women and 176 from men (51 [19 SD] years). Sixty-three percent have had thrombosis, 8% AMI, and 31% PE. Patients with thrombosis had elevated frequency of the C677T polymorphism. The CC genotype was higher than the TT genotype ( P = .003) and CT versus the TT ( P = .009). In patients with PE, the CC genotype was higher than the TT genotype ( P = .038). Pulmonary embolism with massive and submassive events had predominant genotypes 677 TT ( P = .003) and the AA 1298 ( P = .017). Elevated Hcy levels in the presence of the T allele in the C677T gene and of the A allele in the A1298C gene are associated with AMI and massive and submassive PE.

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“…33 In our series, this combination was present in patients having non-Hodgkin lymphoma and this finding would deserve to be further investigated. 34…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms C677T and A1298C of MTHFR Gene: Homocysteine Levels and Prothrombotic Biomarkers in Coronary and Pulmonary Thromboembolic Disease

Lupi‐Herrera

Soto

Lugo-Dimas

et al. 2018

Clin Appl Thromb Hemost

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“…Faganel et al confirmed that MTX clearance decreased to 73.8% in in childhood ALL and malignant lymphoma with the (29). Therefore, patients carrying variant alleles might have an increased risk of developing higher intolerance to MTX (14). The elimination of MTX mainly relies on kidney and liver.…”

Section: Mthfr C677tmentioning

confidence: 99%

“…The negative effects of polymorphism C677T might be explained by the decreased MTHFR activity. In the case of C677T, C nucleotide is substituted by T nucleotide at position 677, resulting in an amino acid exchange from alanine to valine in the respective amino acid sequence, which lowers the affinity of the enzyme for its cofactor, flavin adenine dinucleotide (5,14). As a result, individuals in mutant status (C677T and T677T) exhibit 60 and 30% of the normal MTHFR activity, respectively (4,5).…”

Section: Mthfr C677tmentioning

confidence: 99%

“…In addition, accumulating pharmacogenetic studies have revealed that polymorphisms of enzymes involved in the folate pathway could lead to variability in response to MTX-and HD-MTX-related toxicities in various malignancies (12). For example, single nucleotide polymorphism (SNP) in the gene MTHFR, involved in MTX metabolism, demonstrated associations with a variety of nonhematologic and hematologic malignancies (10,14,15). MTHFR is a key enzyme for intracellular folate homeostasis and metabolism because it catalyzes the irreversible conversion of 5,10methylenetetrahydrofolate (5,10-MTHF), essential for purine and thymidine synthesis, to 5-methyltetrahydrofolate (5-MTHF), essential for protein synthesis and nucleic acid methylation (4).…”

Section: Introductionmentioning

confidence: 99%

“…Jared et al reviewed the studies performed on MTX-induced toxicities across Asian and Caucasian pediatric and adult cancer patients for the MTHFR C677T and A1298C polymorphisms and observed controversial conclusions depending on the patient groups and subgroups investigated in the different systematic reviews as well as the genetic models utilized (7). Also, as most existing studies focused on ALL rather than NHL, there is limited evidence available on the role of C677T and A1298C polymorphisms in HD-MTX-related toxicities in pediatric NHL, with results varying considerably in different studies (10,14,16,17). A multicenter trial NHL-BFM95 with 484 pediatric patients who received 4-or 24-h HD-MTX infusion regimens found that although LBL was significantly associated with MTHFR C677T genotype, this polymorphism did not appear to play a role in the therapy-associated toxicity (18).…”

Section: Introductionmentioning

confidence: 99%

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Influence of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphism on High-Dose Methotrexate-Related Toxicities in Pediatric Non-Hodgkin Lymphoma Patients

Lü

Zhu

et al. 2021

Front. Oncol.

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PurposeThis retrospective study aimed to investigate the relationships between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C and high-dose methotrexate (HD-MTX)-related toxicities in pediatric non-Hodgkin lymphoma (NHL) patients.Patients and MethodsWe reviewed the medical records of 93 NHL patients aged under 18 years who received HD-MTX therapy at the dose of 5 g/m2 with 24-h infusion at Sun Yat-sen University Cancer Center between 2014 and 2019.ResultsThere were 61 males and 32 females, with a median age of 8.8 years (0.9–15.8 years). The tumor types included lymphoblastic lymphoma (n = 38), Burkitt’s lymphoma (n = 31), anaplastic large cell lymphoma (n = 18), diffuse large B-cell lymphoma (n = 6). Overall, 355 courses of HD-MTX therapy were prescribed. All patients were rescued with calcium folinate 12 h after the end of MTX infusion. We found that plasma MTX levels > 0.2 μmol/L at 48 h post-infusion increased the risk of developing oral mucositis (2.4% VS. 9.5%, P = 0.018). Also, patients carrying the C677T and T677T genotypes had tendencies to be more susceptible to oral mucositis (P = 0.034). Patients harboring mutant 677T allele were more likely to develop leucopenia (38.5 vs. 50.3%, P = 0.025) and thrombocytopenia (22.0 vs. 32.4%, P = 0.028). For polymorphism A1298C, the mutant genotype played a protective role in vomiting (11.1 vs. 4.3%, P = 0.018) but increased the risk of anemia (23.8 vs. 41.7%, P < 0.001) and leucopenia (38.1 vs. 50.3%, P = 0.021).ConclusionChildhood NHL patients harboring C677T genotype were more vulnerable to oral mucositis, leucopenia, and thrombocytopenia, while those with A1298C genotype were at a decreased risk of vomiting and more likely to develop anemia and leucopenia.

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Influence of MTHFR C677T and A1298C polymorphisms on the survival of pediatric patients with non-Hodgkin lymphoma

Zhu

et al. 2021

Leukemia & Lymphoma

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C677T and A1298C polymorphisms of methylene tetrahydrofolate reductase in non-Hodgkin lymphoma: southeast Iran

Abstract: Combination of CT and TT genotypes of C677T polymorphism conferred a significantly higher risk for NHL. It is recommended to investigate further the potential role of this polymorphism in NHL development.

Cited by 6 publications

References 33 publications

Polymorphisms C677T and A1298C of MTHFR Gene: Homocysteine Levels and Prothrombotic Biomarkers in Coronary and Pulmonary Thromboembolic Disease

Polymorphisms C677T and A1298C of MTHFR Gene: Homocysteine Levels and Prothrombotic Biomarkers in Coronary and Pulmonary Thromboembolic Disease

Influence of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphism on High-Dose Methotrexate-Related Toxicities in Pediatric Non-Hodgkin Lymphoma Patients

Influence of MTHFR C677T and A1298C polymorphisms on the survival of pediatric patients with non-Hodgkin lymphoma

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