Polymorphisms involved in the folate metabolizing pathway and risk of multiple myeloma.

Folate and methionine metabolism plays an essential role in both DNA synthesis and methylation. Polymorphisms in the genes of the folate-dependent enzymes have been shown to affect disease susceptibility. We conducted a Korean population-based case-control study to evaluate whether genetic variation in folate metabolism may have a role in the risk of multiple myeloma (MM). The study subjects were 173 patients with MM and 1,700 population-based controls. The polymorphisms studied include methylenetetrahydrofolate reductase (MTHFR) 677 C > T and 1298 A > C, methionine synthase (MS) 2756 A > G, methionine synthase reductase (MTRR) 66A > G, thymidylate synthase (TS) 28-bp repeat (2R-->3R) and 6-bp deletion/insertion. MS 2756 AG genotypes were associated with a 1.5-fold lower risk of MM (OR = 0.66, 95%CI; 0.43-0.99, P = 0.047). There was no association between MTHFR C677T, A1298C, MTRR A66G, TS 2R-->3R and 6-bp deletion/insertion polymorphisms and MM. These results suggest that MTHFR C677T, A1298C, MTRR A66G, TS 2R-->3R, and 6-bp deletion/insertion do not significantly factor into the pathogenesis of MM in the Korean population, but that MS A2756G polymorphism may play an important role.