BACKGROUND: Recent studies have provided evidence that common genetic variations with low penetrance could account for a proportion of leukemia and could also influence disease outcome, although the results obtained are still controversial. MATERIAL AND METHODS: We reviewed 54 recent reports focused on the contribution of genetic polymorphisms to the risk of developing leukemia and to disease progression. The polymorphisms of genes encoding drug-metabolising enzymes (CYP family, NQO1, GSTT1, GSTM1, GSTP1), enzymes involved in folate metabolism (MTHFR, TYMS, SHMT1, MTRR), and DNA repair enzymes (XPD, XPG, RAD51, XRCC1, XRCC3, CHEK2, ATM) were considered in the review. RESULTS: There was a good agreement on the influence of NQO1*2 polymorphism and those of the enzymes involved in DNA repair with the increased risk of therapy-related leukemia/myelodysplastic syndrome. Most studies found a strong association between the polymorphisms MTHFR, C677T or A1298C, and NQO1*2 or *3 and the risk of acute lymphoblastic leukemia (ALL). In addition, most of the studies reported an association between GSTT1 deletions and an increased risk of de novo acute myeloid leukemia. In ALL, polymorphisms in the genes of folate metabolism are associated with poor prognosis, and the 3R3R TYMS polymorphism in particular is associated with methotrexate resistance. CONCLUSION: The reports reviewed support the hypothesis that several low-penetrance genes with multiplicative effects together with dietary effects, ambient exposition, and individual immune system responses, may account for the risk of leukaemia.
BACKGROUND: Recent studies have provided evidence that common genetic variations with low penetrance could account for a proportion of leukemia and could also influence disease outcome, although the results obtained are still controversial. MATERIAL AND METHODS: We reviewed 54 recent reports focused on the contribution of genetic polymorphisms to the risk of developing leukemia and to disease progression. The polymorphisms of genes encoding drug-metabolising enzymes (CYP family, NQO1, GSTT1, GSTM1, GSTP1), enzymes involved in folate metabolism (MTHFR, TYMS, SHMT1, MTRR), and DNA repair enzymes (XPD, XPG, RAD51, XRCC1, XRCC3, CHEK2, ATM) were considered in the review. RESULTS: There was a good agreement on the influence of NQO1*2 polymorphism and those of the enzymes involved in DNA repair with the increased risk of therapy-related leukemia/myelodysplastic syndrome. Most studies found a strong association between the polymorphisms MTHFR, C677T or A1298C, and NQO1*2 or *3 and the risk of acute lymphoblastic leukemia (ALL). In addition, most of the studies reported an association between GSTT1 deletions and an increased risk of de novo acute myeloid leukemia. In ALL, polymorphisms in the genes of folate metabolism are associated with poor prognosis, and the 3R3R TYMS polymorphism in particular is associated with methotrexate resistance. CONCLUSION: The reports reviewed support the hypothesis that several low-penetrance genes with multiplicative effects together with dietary effects, ambient exposition, and individual immune system responses, may account for the risk of leukaemia.
Authors: Vanessa S Silveira; Renata Canalle; Carlos Alberto Scrideli; Rosane G P Queiroz; Luiz Fernando Lopes; Luiz Gonzaga Tone Journal: Mol Cell Biochem Date: 2012-01-04 Impact factor: 3.396
Authors: Ana P Azevedo; Susana N Silva; Alice Reichert; Fernando Lima; Esmeraldina Júnior; José Rueff Journal: Pathol Oncol Res Date: 2018-03-14 Impact factor: 3.201
Authors: Yongliang Li; Marie-Jeanne Marion; Jennifer Zipprich; Regina M Santella; Greg Freyer; Paul W Brandt-Rauf Journal: Biomarkers Date: 2009-05 Impact factor: 2.658