Folate metabolism is critical for DNA synthesis and methylation processes. Epidemiological and in vitro evidences suggest that folate is involved in the modulation of cancer risk. The activity of folate pathway enzymes has a pivotal role to assure correct processes related to folate metabolism. Therefore, folate polymorphisms affecting enzyme activity might play a role in cancer risk. Common variants in the genes of MTHFR, MS, MTRR, TS, SHMT, RFC have been investigated in haematological malignancies. Some case-control studies evaluated the association between MTHFR polymorphisms and acute lymphoblastic leukemia (ALL) risk, showing a protective role of 677T and 1298C variants. Protective role has been also ascribed to polymorphisms in MS, MTRR, MTHFD, SHMT and TS genes, although in a small number of studies. In acute and chronic myeloid and in chronic lymphoid leukemia only MTHFR variants have been investigated and no significant modifications in risk evaluation were observed. With regard to lymphoma, studies on non-Hodgkin lymphoma (NHL) reported a protective role of 677T and 1298C variants, whilst other studies showed no association, and an increased risk was found. Controversial results were achieved also for variants in other genes such as MS, TS, RFC, and SHMT and a risk reduction in MTRR 66GG low-grade NHL patients was reported. Altogether, these data indicate an involvment of folate gene variants in haematological malignancies, particularly for ALL cases. The mechanisms by which folate gene variants modulate cancer risk are discussed below.
Folate gene variants and modulation of cancer risk in haematological malignancies
ONGARO, Alessia;DE MATTEI, Monica
2008
Abstract
Folate metabolism is critical for DNA synthesis and methylation processes. Epidemiological and in vitro evidences suggest that folate is involved in the modulation of cancer risk. The activity of folate pathway enzymes has a pivotal role to assure correct processes related to folate metabolism. Therefore, folate polymorphisms affecting enzyme activity might play a role in cancer risk. Common variants in the genes of MTHFR, MS, MTRR, TS, SHMT, RFC have been investigated in haematological malignancies. Some case-control studies evaluated the association between MTHFR polymorphisms and acute lymphoblastic leukemia (ALL) risk, showing a protective role of 677T and 1298C variants. Protective role has been also ascribed to polymorphisms in MS, MTRR, MTHFD, SHMT and TS genes, although in a small number of studies. In acute and chronic myeloid and in chronic lymphoid leukemia only MTHFR variants have been investigated and no significant modifications in risk evaluation were observed. With regard to lymphoma, studies on non-Hodgkin lymphoma (NHL) reported a protective role of 677T and 1298C variants, whilst other studies showed no association, and an increased risk was found. Controversial results were achieved also for variants in other genes such as MS, TS, RFC, and SHMT and a risk reduction in MTRR 66GG low-grade NHL patients was reported. Altogether, these data indicate an involvment of folate gene variants in haematological malignancies, particularly for ALL cases. The mechanisms by which folate gene variants modulate cancer risk are discussed below.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
