Polymorphisms and haplotypes in folate-metabolizing genes and risk of non-Hodgkin lymphoma

Abstract

Folate metabolism plays an essential role in DNA synthesis and methylation processes. Deviations in the flux of folate due to genetic variation could result in selective growth and genomic instability and affect susceptibility to various cancers including lymphoma. To test this hypothesis, genetic polymorphisms in the folate metabolic pathway were investigated using DNA from a population-based case-control study of nonHodgkin lymphoma (

Polymorphisms in xenobiotic‐metabolizing genes and the risk of chronic lymphocytic leukemia and non‐Hodgkin's lymphoma in adult Russian patients

“…MTHFR catalyzes irreversible reduction of 5,10-methylentetrahydrofolate to 5-methyltetrahydrofolate. The most significant polymorphic variants of the MTHFR gene are, probably, C677T and A1298C, which are suggested to modulate the risk to develop different multifactorial diseases including some cancers [14,15,34,35]. The MTRR enzyme participates in transferring of methyl group from 5-tetrahydrophosphate to homocysteine.…”

“…Among potential biomarkers increasing NHL risk two susceptibility alleles in TNF and IL10 have been identified [13]. Several B-CLL and NHL studies have examined polymorphisms involved in folate metabolism; although, results have been inconsistent [14][15][16][17]. Among low-penetrance candidate genes, those involved in xenobiotic metabolism draw a special attention, because they may provide clues to identify potential lymphomagens and to estimate carcinogen effects of environmental pollution.…”

The non-Hodgkin lymphomas: A review of the epidemiologic literature

“…482 Genes involved in the folate metabolism and transport pathway, which affects DNA synthesis and methylation, have been examined in a few NHL case-control studies. [483][484][485][486] Although results are not entirely consistent, findings from these studies suggest that genetic variation in methionine synthase and thymidylate synthase are associated with risk of NHL. Two studies also found that SNPs in the leptin and leptin receptor genes, which participate in regulation of body weight and energy homeostasis, were associated with NHL risk.…”

Implication of the folate-methionine metabolism pathways in susceptibility to follicular lymphomas

“…The genes encoding folate metabolic enzymes display several single nucleotide polymorphisms (SNPs)-for example, methylenetetrahydrofolate reductase (MTHFR C677T and MTHFR A1298C), serine hydroxymethyltransferase (SHMT C1420T), and methionine synthase (MS or MTR A2756G)-and variable number tandem repeats (VNTRs) for thymidylate synthase (TS or TYMS VNTR 2R and 3R). The corresponding common variants decrease or increase the enzymatic activity of the proteins encoded [8][9][10] and have been implicated in the development of adult and childhood acute lymphocytic leukemia (ALL) [11][12][13][14][15][16] and in various other malignancies including endometrial cancer, 17 cervical intraepithelial neoplasia, 18,19 colon cancer, 20 and pancreatic cancer. 21 Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydrofolate (methylene THF) to 5-methyltetrahydrofolate (5-methyl THF), the major circulatory form of folate and carbon donor for the remethylation of homocysteine to methionine (Figure 1).…”