Folate - associations with breast cancer depending on intake, metabolism, genetic variation and estrogen receptor status
Folate is a B-vitamin that may influence cancer development via its role as methyl donor for DNA synthesis and methylation.
Plant foods contain many bioactive compounds including folate and fiber. Results from the Malmö Diet and Cancer (MDC) cohort indicate lower breast cancer risk at high fiber intake. Folate intake may partly explain this association.
Aims of this thesis were to examine if intakes or plasma concentrations of folate are associated with postmenopausal breast cancer risk, and if associations depend on genetic variation of the folate metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) or estrogen receptor α and β expression of tumors.
Food habit information and blood samples were collected 1991-96 from 17 035 women between 45 and 73 years in the MDC study. Until end of 2004, 544 cases of invasive breast cancer were diagnosed.
High folate intake was associated with lower breast cancer risk. The MTHFR 677T allele was associated with increased risk. Among women with this allele, the risk increased with higher intakes and plasma concentrations of folate, and was especially pronounced for folate supplement consumers. Estrogen receptor β negative (ERβ-) breast cancer increased with higher plasma folate concentrations independently of 677C>T genotype.
The results encourage consumption of folate rich foods. However, since women with disturbed folate metabolism due to genetic predisposition may respond differently to high intakes, and high folate status may promote development of ERβ- tumors, folate supplements should be cautiously recommended. The results also contribute knowledge to current discussions regarding mandatory folate fortification of foods.