Methylenetetrahydrofolate reductase polymorphisms in myeloid leukemia patients from Northeastern Brazil

Abstract

Methylenetetrahydrofolate reductase (MTHFR: EC 1.5.1.20) polymorphisms are associated to acute lymphoid leukemia in different populations. We used the polymerase chain reaction and the restriction fragment length polymorphism method (PCR-RFLP) to investigate MTHFR C677T and A1298C polymorphism frequencies in 67 patients with chronic myeloid leukemia (CML), 27 with acute myeloid leukemia FAB subtype M3 (AML-M3) and 100 apparently healthy controls. The MTHFR mutant allele frequencies were as follows: CML = 17.2% for C677T, 21.6% for A1298C; AML-M3 = 22.2% for C677T, 24.1% for A1298C; and controls = 20.5% for C677T, 21% for A1298C. Taken together, our results provide evidence that MTHFR polymorphisms have no influence on the development of CML or AML-M3

Polymorphisms of the Methylene Tetrahydrofolate Reductase and Susceptibility to Acute Lymphoblastic Leukemia in Children

“…However, there is little known about the exact mechanism of tumorigenesis in ALL, and the interactions between genetic and environmental risk factors are the most probable causes. 1 Due to the incorrect DNA synthesis or altered methylation status of oncogenes and/or tumor suppressor genes, several genetic alterations have been identified in the pathogenesis of lymphoid malignancies. 2 Since folate metabolism involves DNA methylation and nucleotide synthesis, it seems that folate metabolism may play an important role in carcinogenesis.…”

Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population

“…Polymorphic variants of several genes, diet, environmental exposure to carcinogens and individual immune system's characteristics are potential factors that increase predisposition to leukemia (Bowen et al, 2003). Association studies have been performed to identify genetic variants associated with CML susceptibility, and among them are methylenetetrahydrofolate reductase (MTHFR) (Hur et al, 2006;Moon et al, 2007;Barbosa et al, 2008), glutathione S-transferases (GSTs) (Hishida et al, 2005;Souza et al, 2008), and haptoglobin (Hp) gene polymorphisms (Nevo and Tatarsky, 1986;Campregher et al, 2004).…”

“…However, under situations of decreased MTHFR activity, more MTHFR substrate is available for purine and pyrimidine synthesis, which may prevent imbalances of nucleotide pools during DNA synthesis and potentially oncogenic alterations in DNA methylation (Ma et al, 1997;Ulrich et al, 1999). Associations have been described between the common MTHFR polymorphisms C677T and A1298C and risk of leukemia (Skibola et al, 1999;Franco et al, 2001;Robien and Ulrich, 2003;Robien et al, 2004;Ismail et al, 2009), but few studies with CML have been published, with inconsistent results (Robien and Ulrich, 2003;Robien et al, 2004;Hur et al, 2006;Moon et al, 2007;Barbosa et al, 2008;Ismail et al, 2009). Therefore, studies in several ethnicities are required to better understand the biological significance of these polymorphisms in CML susceptibility, since they vary among ethnic groups (Franco et al, 1999;Robien and Ulrich, 2003).…”

Differential effects of the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) on hematological malignancies among Latinos: a meta-analysis

“…Eight publications were not case-control studies, two publications lacked sufficient information, and one publication used previously published data; therefore, these 11 publications were excluded. This resulted in 13 publications (15 studies) that were included in this meta-analysis (Franco et al , 2001; Zanrosso et al , 2005, 2006; da Costa Ramos et al , 2006; Ruiz-Argüelles et al , 2007; Amorim et al , 2008; Barbosa et al , 2008; Gallegos-Arreola et al , 2008; Lima et al , 2008; Metayer et al , 2011; Lordelo et al , 2012; Silva et al , 2013; Gutiérrez-Álvarez et al , 2016), and three studies from Mexico (Ruiz-Argüelles et al , 2007; Gallegos-Arreola et al , 2008; Gutiérrez-Álvarez et al , 2016). One study focused on Latinos living in the USA (Metayer et al , 2011).…”