Folate has important roles in DNA synthesis and repair. Folate deficiency is thought to contribute to increased risk of cancer through increased DNA strand breaks, impaired DNA repair, and increased mutagenesis. U.S. food manufacturers are required to add folic acid to white flour, enriched pasta, and cornmeal. This is to ensure that pregnant women receive enough of this B vitamin in order to reduce the risk of neural tube defects in their babies.
Differences in response to folate may have genetic basis
Population studies have reported inconsistent results with respect to folate and breast cancer. These contradictory results suggest that different subgroups may experience varying outcomes from folic acid supplementation, and, given folate's role in DNA synthesis and repair, that these differences may have a genetic basis. There is some evidence for this.
A Swedish study which examined plasma folate concentration in relation to genotypes of a folate-metabolizing enzyme found a genetic variant that was associated with high circulating folate levels. This variant was also associated with increased breast cancer risk. In women with other genotypes, no significant associations between breast cancer and folate levels were observed. A Singapore Chinese study which examined the relationship between green tea (which reduces folate absorption) and risk of breast cancer found that the effect of folate consumption varied based on whether the women possessed certain genotypes.
Folic acid supplements normally are unnecessary in the U.S.
Some studies have linked adequate folic acid to a decrease in neuroblastomas, leukemia, some brain tumors, and colon cancer. Approximately 10% of the U.S. population overall (and a higher percentage of the poor) is estimated to have a level of folate deficiency sufficient to cause chromosome breaks. It is unclear how folic acid supplementation influences breast cancer risk in populations with low levels of folate deficiency. However, based on laboratory evidence, folic acid supplementation and food fortification may prevent the initiation of breast cancer in normal tissues.
On the other hand, folic acid supplementation might promote the progression of existing tumors in some women. In fact, folic acid has been shown to reduce the expression of beneficial tumor suppressor genes in breast cancer cells. Now a new study has reported that folic acid supplementation promotes tumor progression in an animal model of breast cancer.
Food sources of folate
The following foods are good sources of folate, as well as being associated with reduced risk of breast cancer:
Note that both green tea and black tea reduce intestinal absorption of folate and should not be consumed simultaneously with high-folate foods by those wishing to increase their folate levels.
Latest research finds folate promotes mammary tumor growth and metastasis
The study referenced at the beginning of this news story was designed to investigate whether folic acid supplementation can promote the progression of established precancerous or cancerous mammary lesions. This is a critically important issue, according to the authors, since breast cancer patients and survivors in the U.S. and Canada are typically exposed to high levels of folic acid due to folic acid fortification of foods and widespread supplement use.
To conduct the study, the authors used mammary tumor-prone Sprague-Dawley rats who were administered a carcinogen at puberty. When the initial tumor reached a predetermined size, the animals were divided into groups to receive various levels of folic acid or a control diet for up to 12 weeks. Mammary tumor growth was monitored weekly. At the end of the study period, all mammary tumors were analyzed. The effect of folic acid on the expression of proteins involved in tumor proliferation, apoptosis (programmed cell death), and mammary tumorigenesis was determined in representative tumors.
The authors did not find a linear correlation between the dosage of folic acid received and its tumor-promoting effects in the animals. However, folic acid supplementation was clearly found to promote the progression of the mammary tumors (including significantly higher tumor weight and volume compared with rats on the control diet). The most significant and consistent mammary tumor-promoting effect was observed in rats given the lowest dosage of folic acid tested. Folic acid was also associated with an increased expression of HER2. The authors conclude that folic acid supplementation may promote the progression of established mammary tumors, a finding that needs further clarification in breast cancer patients and survivors.