An estimated 600,000 cases of breast and colorectal cancer a year worldwide-160,000 in the United States-could be prevented by increasing peoples' serum level of vitamin D, according to a new study from the Moores Cancer Center at the University of California, San Diego. It was published in the August issue of the journal Nutrition Reviews.
National report - An estimated 600,000 cases of breast and colorectal cancer worldwide each year - including 160,000 in the United States - could be prevented by increasing peoples' serum level of vitamin D, according to a new study from the Moores Cancer Center at the University of California, San Diego, published in the August issue of the journal Nutrition Reviews.
The response is not a straight line or smooth curve, but rather a series of plateaus where a certain minimal level of 25(OH)D is required to afford any protection, researchers say. The plateau varies by the type of cancer and is associated with the density of expression of vitamin D receptors on cells in individual tissue compartments.
The problem is that most Americans' serum levels fall far below those levels during the winter months, and many people do not even achieve them during the summer.
Dr. Garland says the human species evolved in the tropics, where exposure to solar radiation was an everyday event that generated high levels of vitamin D. But as man migrated away from the tropics, adapted clothing, and in recent generations moved from an outdoor to an indoor workplace, levels of serum vitamin D have fallen precipitously.
"The modern lifestyle simply does not meet the biologic need that evolved thousands of years ago," he says. Even his own bucolic clime of San Diego is not exempt. The intensity of solar radiation in winter is not sufficient to generate adequate levels of 25(OH)D, he says.
Persons are likely to have a serum level of 20 to 24 ng/ml unless they supplement or have sufficient skin exposed at midday. That has contributed to increased incidence of cancers.
Mechanism of action
Dr. Garland calls vitamin D "a magic key to the action of a lot of genes" - it modulates the actions of at least 160 of them. The cellular vitamin D receptor chain is very large and quite redundant. It is ubiquitous and likely reflects an early role in the evolution of life, he says.
His work is focusing on the role of vitamin D in maintaining intercellular junctions. It ties into the hypothesis that one mechanism of action of cancer is in the cell membrane rather than its DNA in the nucleus.
"The tight junction of cells in tissue, each pressing against the other, exerts a stability on the tissue and inhibits the development of malignancies," he says.
"What we are proposing is that loss of contact inhibition allows the ancestral (unicellular) growth program in the cell to be enabled, and they begin to proliferate. Those cells are able to move around a little, enough so that they can begin to compete with one another for survival," he says.
"In that setting, cells that have even a slight advantage do better each generation. Unfortunately, those often are the precursors of cancer," Dr. Garland says.
Over the course of 9,000 to 10,000 generations - perhaps 20 to 30 years - that can become a palpable mass. Dr. Garland calls it "a natural evolutionary process that takes place over a long period of time." By the time the mass is palpable, it is usually clonal, the offspring of a single ancestor through a long series of steps.
Dr. Garland says supplementation and sensible exposure to solar radiation can generate serum levels of 25(OH)D that tighten cellular junctures and inhibit the development of tumors.