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Vitamin D deficiency contributes to spread of breast cancer in mice, Stanford study finds

Breast tumors in laboratory mice deficient in vitamin D grow faster and are more likely to metastasize than tumors in mice with adequate levels of vitamin D, according to a preliminary study by researchers at the Stanford University School of Medicine.

The research highlights a direct link between circulating vitamin D levels and the expression of a gene called ID1, known to be associated with tumor growth and breast cancer metastasis.

The finding builds upon several previous studies suggesting that low levels of vitamin D not only increase a person’s risk of developing breast cancer, but are also correlated with more-aggressive tumors and worse prognoses. Although the research was conducted primarily in mice and on mouse cells, the researchers found in a study of 34 breast cancer patients that levels of circulating vitamin D were inversely correlated with the expression levels of ID1 protein in their tumors, and they confirmed that a vitamin D metabolite directly controls the expression of the ID1 gene in a human breast cancer cell line.

“Although much more research needs to be done, research from our lab and others suggests that people at risk for breast cancer should know their vitamin D levels and take steps to correct any deficiencies,” said Brian Feldman, MD, PhD, assistant professor of pediatrics.

Feldman, who is a Bechtel Endowed Faculty Scholar, is the senior author of the study, which was published online March 2 in Endocrinology. Lead authors of the work are graduate student Jasmaine Williams and postdoctoral scholar Abhishek Aggarwal, PhD.

Confusion about optimal dosage

The researchers emphasize that their findings don’t imply that more vitamin D is always better. Correcting a deficiency is very different from taking more than the recommended dosage, which the Institute of Medicine says is 600 international units per day for people age 70 and younger, and 800 IU for older adults. Excess levels, variously estimated to occur at about 4,000 to 10,000 IU per day, have been linked to damage to the kidneys, cardiovascular system and other organs.

Not all medical organizations agree on the optimal amount of vitamin D. The confusion stems in part from the fact that, although it can be ingested via food and nutritional supplements, our bodies can also make vitamin D with the help of ultraviolet rays from the sun. So it’s difficult to know exactly how much any individual may need to take as a supplement, and that amount can vary throughout the year. Those who don’t get enough sun exposure, or people with darker skin, are more likely than fair-skinned individuals who spend time outdoors each day to be deficient. The use of sunscreen can also affect vitamin D synthesis.

Once ingested or made by the body, vitamin D is converted through a series of steps into its active form, calcitriol. Calcitriol binds to a protein in cells called the vitamin D receptor, which then enters the cell’s nucleus to control the expression of a variety of genes, including those involved in calcium absorption and bone health.