UPDATE - Issue 09 - October 2001
Vitamin D and Prostate Cancer
Gren Oades talks about the research he is doing at St. George's Hospital
Despite the vast amounts of time and money spent on researching treatments for prostate cancer over the past 30 years there has been little impact on overall survival with this disease over this time. Prostate cancer remains the second most commonly diagnosed malignancy in men in this country and as the population ages its incidence is rising. There is now a shift in emphasis in prostate cancer towards earlier diagnosis and treatment. It is widely accepted that there is a natural progression of prostate cells from normal through hyperplastic and a recognised pre-cancerous stage to frank malignancy and metastatic disease. As a policy of prevention could conceivably lead to less morbidity with an improved survival, arresting this pathway has become a very attractive target for therapy.
Vitamin D is, like testosterone, a hormone. Its precursor is produced in the skin from cholesterol under the influence of ultraviolet energy from sunlight. It is altered by the body's metabolism first in the liver and then in the kidney to produce an active form, 1,25-dihydroxyvitamin D3. Classically, vitamin D has been thought to act solely upon bone, intestine, kidney and parathyroid to regulate calcium and phosphate levels in the body. Only recently has it been noted that a number of other organs, including the prostate, express the vitamin D receptor. By binding to this receptor vitamin D has recently been shown to have wide ranging effects on growth and differentiation in many different organs.
In 1990 Gary Schwartz and his colleagues proposed that a low level of circulating 1,25-dihydroxyvitamin D3 was a risk factor for prostate cancer. Epidemiological evidence suggests that many of the major risk factors for this disease can be explained by Schwartz' hypothesis. Mortality rates in the United States are higher in northern latitudes and inversely correlate with the availability of ultraviolet light and hence levels of vitamin D in the body. People of older age have lower circulating levels of this hormone and suffer more from prostate cancer. The hypothesis may also offer a potential partial explanation for the increased risk of African American men to develop prostate cancer as a result of their darker skin pigmentation impairing vitamin D synthesis.
Changes in the vitamin D receptor, which alter its function, may contribute to an individual's risk of prostate cancer. The gene for the vitamin D receptor has a number of recognised polymorphisms. This means that there are a number of distinct genes for the vitamin D receptor with potentially different functions that, like eye colour, can be inherited within a population with each person receiving only one type. Research here at St. George's Hospital, South West London aims to identify if these different types of vitamin D receptor alter an individuals risk of getting prostate cancer or of developing a more aggressive form.
In future it may be possible to identify people at high risk of prostate cancer and reduce this by modifying the vitamin D content of their diet. The vitamin D receptor type of a person with early prostate cancer may help decide the correct form of treatment they should be offered. If analogues of vitamin D can be developed that have less effect on the body's calcium levels they may even lead to new treatments for advanced disease.