Aktuelle Neurologie 2009; 36 - P642
DOI: 10.1055/s-0029-1238735

Genetic variants of folate and methionine metabolism and primary central nervous system lymphoma incidence in a German cohort of 185 patients

D Kurzwelly 1, S Knop 1, J Löffler 1, A Korfel 1, E Thiel 1, H Hebart 1, M Weller 1, M Linnebank 1, U Herrlinger 1
  • 1Bonn, Würzburg, Berlin, Mutlangen; Zürich, CH

Objective: Functional genetic polymorphisms of folate and methionine metabolism play an important role in DNA synthesis and methylation, and affect the risk of various cancers including lymphoproliferative disorders. In a retrospective analysis of 185 immunocompetent patients with primary central nervous system lymphoma (PCNSL) and 212 population controls we therefore investigated eight polymorphisms in folate-metabolizing genes for a potential association with the development of PCNSL.

Methods: Genotyping was performed by amplification of genomic DNA applying polymerase chain reaction (PCR) and subsequent restriction enzyme digestion or by allele specific PCR, followed by agarose gel electrophoresis. The two-sided Pearson's Chi2 test was used to analyze the distribution of the respective genotypes in the patient and the control group for statistical significance. Multinominal logistic regression analysis was applied to test the independent predictive value of the tested polymorphisms with respect to PCNSL formation.

Results: We observed an underrepresentation of the G-allele of the methyltetrahydrofolate homocysteine S-methyltransferase (MTR) c.2756A>G (D919G) missense dimorphism among PCNSL patients (p=0.045). Furthermore, for the methylenetetrahydrofolate reductase (MTHFR) c.1298A>C (E429A) polymorphism the mutated C-allele was found more frequently among PCNSL patients in comparison to population controls (p=0.026). There were no associations of the other polymorphisms investigated [MTHFR c.677C>T, transcobalamin 2 (Tc2) c.776C>G, cystathionin β-synthase (CBS) c.844ins68, reduced folate carrier-1 (RFC-1) c.80G>A, thymidylate synthase (TYMS) 28-bp repeat, and dihydrofolate reductase (DHFR) c.594+59del19bp] and the development of PCNSL.

Conclusions: The present analysis is the largest to date to evaluate associations between genetic variants of folate and methionine metabolism and PCNSL incidence. Our results support the hypothesis that folate and methionine metabolism is relevant for the susceptibility to PCNSL.