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Blood, 1 July 2006, Vol. 108, No. 1, pp. 278-285.
Prepublished online as a Blood First Edition Paper on January 12, 2006; DOI 10.1182/blood-2005-04-1567.
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Submitted April 18, 2005
Accepted December 29, 2005
Implication of the folate-methionine metabolism pathways in susceptibility to follicular lymphomas
Sidonie Niclot, Quentin Pruvot, Caroline Besson, Daniel Savoy, Elisabeth Macintyre, Gilles Salles, Nicole Brousse, Bruno Varet, Paul Landais, Pierre Taupin, Claudine Junien*, and Dominique Baudry-Bluteau
Inserm UR383, Paris, France
Service d'Hematologie Clinique Adulte, Hopital Necker-Enfants Malades, Universite Rene Descartes, Paris, France
Laboratoire d'Hematologie, Hopital Necker-Enfants Malades, Universite Rene Descartes, Paris, France
Service d'Hematologie-Centre Hospitalier Lyon Sud, Pierre-Benite, France
Service d'Anatomo-pathologie, Hopital Necker-Enfants Malades, Universite Rene Descartes, Paris, France
Departement de biostatistiques, Hopital Necker-Enfants Malades, Universite Rene Descartes, Paris, France
* Corresponding author; email: junien{at}necker.fr.
The incidence of follicular lymphoma (FL) in industrialized countries has been increasing since the 1950s. Polymorphisms in genes encoding key enzymes controlling folate-methionine metabolism including methylenetetrahydrofolate reductase (MTHFR), methionine synthase, (MS/MTR), serine hydroxymethyl transferase (SHMT) and thymidylate synthase (TS/TYMS) modify the risk of various cancers, and possibly FL. This study is specifically looking for an association between MTHFR, MTR, TYMS and SHMT polymorphisms and the risk of FL. We carried out a case-control study with 172 patients diagnosed with FL and 206 control subjects. We report that the risk of FL was doubled by the association of one mutant allele at both MTHFR polymorphisms. MTR 2756AA individuals had 2-fold higher risk of FL and subjects not having at least one TYMS 2R allele showed a 2-fold higher risk of FL. The MTR 2756AA genotype conferred a greater multivariate-adjusted relative risk of FL, and the risk was multiplied by almost 5 in the TYMS2R(-)/MTR 2756AA combination. In conclusion, common polymorphisms in key enzymes of the folate-methionine metabolism pathway result in an increased risk of FL and suggest that inadequate intake of dietary folate and other methyl donor nutrients may contribute to the development of this malignancy.
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