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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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NEOPLASIA

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

From the Institut National de la Santé et de la Recherche Médicale (INSERM) UR383-E0210, the Service d'Hématologie Clinique adulte-U550, Laboratoire d'Hématologie, Service d'Anatomo-pathologie, and the Département de biostatistiques, Hôpital Necker-Enfants Malades, Université René Descartes, Paris, France; and the Service Hématologie-Centre Hospitalier Lyon Sud, Lyon, France.

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 or MTR), serine hydroxymethyltransferase (SHMT), and thymidylate synthase (TS or TYMS), modify the risk of various cancers and possibly FL. This study specifically looks 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. Individuals with MTR 2756AA 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. (Blood. 2006;108:278-285)


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Related Article in Blood Online:

Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER Case-Control Study
Unhee Lim, Sophia S. Wang, Patricia Hartge, Wendy Cozen, Linda E. Kelemen, Stephen Chanock, Scott Davis, Aaron Blair, Maryjean Schenk, Nathaniel Rothman, and Qing Lan
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