Increased folate may slash breast cancer risk

Writing in the current issue of the American Journal of Clinical Nutrition , the researchers state that fruit and vegetables may be a better option to increase folate consumption, and raise questions about folic acid fortification.

"Sweden has not yet come to a decision concerning the mandatory folic acid fortification of foods," wrote the authors, led by Ulrika Ericson from Lund University.

"With regard to the contradictory results from different studies, including an American study that indicated an increased risk at total intakes much higher than in our study an increased consumption of fruit and vegetables would be a safer way to increase folate intakes."

Folate is found in foods such as green leafy vegetables, chick peas and lentils, and an overwhelming body of evidence links has linked folate deficiency in early pregnancy to increased risk of neural tube defects (NTD) - most commonly spina bifida and anencephaly - in infants.

The researchers investigated if there was an association between folate intake and invasive breast cancer risk in 11,699 postmenopausal women over the age of 50.

Dietary assessments were done at the start of the study using seven-day diet records, a 168-item food-frequency questionnaire, and an interview about dietary habits.

After 9.5 years of follow-up, 392 cases of breast cancer had been diagnosed.

The average folate intake for the women was 238 micrograms per day, and 19 per cent of subjects used folic acid supplements.

The researchers calculated that women in the highest average intake group (456 micrograms of folate per day) had a 44 per cent lower risk of invasive breast cancer than women in the lowest average intake group (160 micrograms of folate per day).

The benefits were still observed after the researchers took into account the intake of other B vitamins, age, physical activity, smoking, alcohol use, and the use of hormone replacement therapy.

However, when the women were divided into normal weight women (BMI of less 25 kg per sq. m) and overweight women (BMI of more than 25), the researchers report that the protective effect of folate only applied to the overweight women.

"Our findings of an association between high folate intake and lower breast cancer incidence confirm the biological hypothesis that low intakes of folate enhance the development of breast cancer," wrote the researchers.

They went on to explain that the reduced form of folate, 5- Methyltetrahydrofolate (MTHF) plays a role in a series of reactions for DNA methylation "Changes in DNA methylation patterns are an early event in carcinogenesis and may influence gene silencing," they said.

"Folate is also involved in DNA synthesis and repair; folate deficiency has been related to elevated uracil incorporation to DNA and subsequent chromosome breaks, which may contribute to an increased risk of cancer."

An accompanying editorial by Cornelia Ulrich from the Fred Hutchinson Cancer Research Center, Seattle, said that the study added a new chapter to the ongoing folate story.

"The question arises as to why much stronger inverse trends were seen in the Swedish cohort than in previous largely United States-based cohort studies," wrote Ulrich.

"The Swedish study population, of which only 19 per cent are supplement users, had lower intakes of folate than did the US populations previously studied.

If only a very low folate status increases the risk of invasive breast cancer, then strong associations can be detected only in study populations that include a sufficient number of subjects in the low-folate range."

Ulrich added a note of caution for increasing folate intakes in the general population as part of public health measures, as has been adopted by the US, Canada and Chile for the prevention of neural tube defects.

"The success of this policy [for neural tube defects] is indisputable," she said.

"At the same time, unmetabolized folic acid is detectable in the circulation of healthy individuals, with unknown physiologic consequences.

Several European countries are currently considering the introduction of folic acid fortification for the prevention of neural tube defects, perhaps under the assumption that folic acid fortification will also aid in the prevention of cancer and of cardiovascular disease.

"Yet, there is now increasing evidence from randomized trials that high doses of folic acid can foster the growth of common precancerous lesions.

The benefit of reducing a relatively small number of neural tube defects may be outweighed by the possible negative effects on tumor promotion in a substantial fraction of the population.

"Thus, a cautionary approach is warranted as we consider whether to recommend an increase in folate status for all," concluded Ulrich.

Over one million women worldwide are diagnosed with breast cancer every year, with the highest incidences in the US and the Netherlands.

The National Cancer Institute estimates that 13 percent of American women will develop breast cancer during their lives.

Source: American Journal of Clinical Nutrition Volume 86, Pages 434-443 "High folate intake is associated with lower breast cancer incidence in postmenopausal women in the Malmo Diet and Cancer cohort" Authors: U. Ericson, E. Sonestedt, B. Gullberg, H. Olsson, and E. Wirfalt