Prophylactic folic acid in pregnancy has been found to reduce the subsequent incidence of acute lymphoblastic leukaemia (ALL) in childhood. A significant negative association has also been found with the MTHFR 677(CT) polymorphism and leukaemias with MLL translocations, but a positive association with hyperdiploidy in infants with ALL or acute myeloid leukaemia or with childhood ALL. A second polymorphism in the MHTFR gene, A1298C, is also strongly associated with hyperdiploid leukaemia. Neither polymorphism is associated with the TEL-AML1 fusion. There are various positive and negative associations between polymorphisms in folate-dependent enzymes and the incidence of adult ALL.
The C677T polymorphism is thought to lead to increased thymidine pools and 'better quality' of DNA synthesis by shunting one-carbon groups towards thymidine and purine synthesis. This may also explain its reported association with a lower risk for colorectal cancer. The incidence of colon cancer was also lower in subjects taking vitamin supplements containing folic acid and with higher folate intake compared with control subjects in the Nurses Health Study. Other tumours that have been associated with folate polymorphisms or status include follicular lymphoma, breast cancer and gastric cancer.
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