2.5. B-vitamins, folate
Folate, originating mainly from green leafy vegetables and fruits,is an important B vitamin required for DNA synthesis, and it is alsoinvolved in the methionine metabolic pathway, which is crucial forDNA methylation. Thus, one-carbon metabolism can impact bothgenetic and epigenetic pro-carcinogenic processes, and these bio-logic roles potentially make folate and other related B vitaminsimportant in cancer prevention [27].The associations between B vitamins and breast cancer havebeen extensively studied and the associations are complex. Epi-demiological studies on the association between folate intakeestimated through questionnaires and breast cancer risk have pro-vided mixed results [28]. Protective effects have been observedin populations with low folate status, in which vitamin supple-mentation is infrequent [29]. The WCRF report concluded that theepidemiological data for an association between folate and breastcancer risk was too limited to allow conclusions to be reached.Issues that required further consideration included interactionbetween B vitamins and genetic background, and some lifestylefactors such as alcohol intake.Like for other dietary components, additional factors mayimpact the relationship between folate intake and breast cancerrisk, such as alcohol intake, and polymorphisms in methylenetetra-hydrofolate reductase (MTHFR), which codes for a key one-carbonmetabolizing protein. Further, the impact of folate may be relatedto the tumor type since the incidence of the estrogen receptor betanegative breast cancers is increased in women in the highest tertileof plasma folate compared to the lowest [30].