A Prospective Study of Folate Intake and the Risk of Breast Cancer
Abstract & Commentary
Synopsis: In women who consumed more than 15 g/d of alcohol from any source, the increased relative risk of breast cancer was reduced if folate intake was 600 g/d.
Source: Zhang S, et al. JAMA 1999;281:1632-1637.
This study used the nurses’ health study cohort to test the hypothesis that "higher folate intake might reduce the risk of breast cancer, particularly among women with greater alcohol consumption, which itself moderately increases breast cancer risk." The rationale for this hypothesis is that alcohol is a known folate antagonist and folate is required for DNA repair mechanisms. Therefore, chronic alcohol use might induce a relative folate deficiency and predispose that individual to faulty DNA repair and cancer. Zhang and colleagues were not able to look at these relationships in women known to be at risk for faulty DNA repair mechanisms (i.e., BRCA1 and BRCA2 carriers.) The study methodology is described in exacting detail and is adequate to address the query as posed. The diet information was collected by questionnaire initially in 1980 and then at subsequent timepoints. Higher folate intakes ( > 400 g/d) in general did not reduce the risk of invasive breast cancer. Higher folate intakes typically were achieved via daily multivitamin ingestion. In women who consumed more than 15 g/d of alcohol from any source (12 ounces of beer contains 12.8 g; 4 ounces of wine 11.0 g, and 1.5 ounces of spirits 14.0 g), the increased relative risk of breast cancer (RR = 1.24, CI 1.11 - 1.39) was reduced if folate intake was 600 g/d. This relationship held in both premenopausal and postmenopausal women.
COMMENT By Sarah L. Berga, MD
No longer is folate the obstetrician’s vitamin. Folate is forever! Adequate folate intake is implicated in the chemoprevention of neural tube defects, colorectal cancer, cardiovascular disease, and now breast cancer associated with higher alcohol intakes. Folate takes its name from foliage, as in green leafy vegetables. But the predominant source in most American diets is fortified breakfast cereal and multivitamins. Fortunately, these sources provide a highly bioavailable form of folate, so the strategy of food fortification and multivitamin use in this context appears to be a wise one.1 Folate from food sources such as orange juice and vegetables is labile (destroyed by food processing and exposure to heat and air). Also, absorption from food can be hindered by other components of the food matrix. Based on this and other similar studies, it makes sense to hedge bets and recommend adequate folate intake, not only to pregnant women and those contemplating conception, but to all women, especially those who drink alcohol regularly.
I wonder how many physicians regularly ask their patients about habits of daily living, such as smoking, alcohol intake, diet in general, vitamin and supplement use in particular, and exercise. There is so much to cover when in the office and so little time. To a great extent, we are dependent on patients to raise issues of importance to them. For example, when a patient asks me about hormones and breast cancer, not only do I tell her that it is unlikely that postmenopausal hormone use is a major promoter of breast cancer, I also use this opportunity to ask about alcohol intake. I explain that small amounts of alcohol are also unlikely to promote breast cancer, but that larger amounts may. However, not all women see a physician on a regular basis. Thus, it also would be a good idea to conduct a campaign to raise the nutrition IQ of doctors and patients alike with the goal of getting us to obtain most of our nutrients from food. Since this strategy is expensive, variably effective, and time-consuming, shortcuts have been advocated and effected. These shortcuts are multivitamin use and food fortification. For certain nutrients, such as folate, vitamin E, and vitamin D, these shortcuts make sense. However, just as it may be unrealistic to expect everyone to get everything they need nutritionally from food, I like to remind patients that it is also unrealistic to expect to get all the nutrients they need from food supplements and multivitamins. There is no substitute for a good diet if for no other reason than the fact that we do not know everything there is in food that we need. Until we get much smarter and can readily individualize nutritional advice, I suggest that the best strategy is to take an inexpensive multivitamin (i.e., one that contains types and amounts of vitamins within the recommended ranges) and eat according to the newest food group pyramid. (Dr. Berga is Associate Professor, Departments of Obstetrics, Gynecology, Reproductive Sciences, and Psychiatry, University of Pittsburgh.)
Reference
1. Jacques PF, et al. N Engl J Med 1999;340:1449-1454.
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