MTR and MTRR polymorphisms, dietary intake, and breast cancer risk.

Methionine, the precursor for the universal methyl donor, S-adenosylmethionine, is produced through the irreversible transfer of a methyl group from 5-methyltetrahydrofolate. This reaction is regulated by two enzymes, methionine synthase (MTR) and methionine synthase reductase (MTRR). MTR is polymorphic at nucleotide 2,756 (A-to-G) and has been associated with decreased plasma homocysteine levels (1-3). MTRR is polymorphic at nucleotide 66 (A-to-G) and the variant has a lower affinity for MTR (4) and is inconsistently associated with homocysteine level (5-7), although it is a risk factor for neural tube defects (8) and Down syndrome (9) in conditions of higher homocysteine. There is no report on either MTR or MTRR in relation to breast cancer risk. In an extension of our previous reports that folate intake was inversely associated with breast cancer risk (10) and that this association was particularly strong among women with the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype (11), we investigated whether these associations may be modified by MTR and MTRR genotypes.