PHILADELPHIA -- Vitamin D deficiency was an indicator of aggressive prostate cancer and spread of the disease in European-American and African-American men who underwent their first prostate biopsy because of abnormal prostate-specific antigen (PSA) and/or digital rectal examination (DRE) test results, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.
"Vitamin D is a steroid hormone that is known to affect the growth and differentiation of benign and malignant prostate cells in prostate cell lines and in animal models of prostate cancer," said Adam B. Murphy, M.D., MBA, assistant professor in the Department of Urology at the Northwestern University Feinberg School of Medicine in Chicago. "In our study, vitamin D deficiency seemed to be a predictor of aggressive forms of prostate cancer diagnosis in European-American and African-American men.
"The stronger associations in African-American men imply that vitamin D deficiency is a bigger contributor to prostate cancer in African-American men compared with European-American men," added Murphy. "Vitamin D supplementation may be a relevant strategy for preventing prostate cancer incidence and/or tumor progression in prostate cancer patients."
The most accurate way to measure how much vitamin D we have in our body is to measure levels of 25-hydroxyvitamin D (25-OH D) in our blood. The normal range of 25-OH D is 30 to 80 nanograms per milliliter (ng/ml).
In this study, European-American and African-American men had 3.66 times and 4.89 times increased odds of having aggressive prostate cancer (Gleason grade of 4+4 or higher), respectively, and 2.42 times and 4.22 times increased odds of having tumor stage T2b or higher, respectively, if their 25-OH D levels were less than 12 ng/ml at the time of prostate biopsy. In addition, African-American men had 2.43 times increased odds of being diagnosed with prostate cancer, if their 25-OH D levels were less than 20 ng/ml.
Between 2009 and 2013, Murphy and colleagues enrolled 667 men, ages 40 to 79 years, who were undergoing their first prostate biopsy at one of five urology clinics in Chicago following an abnormal PSA or DRE. Serum 25-OH D levels were measured at recruitment. Of the study participants, 273 were African-American and 275 were European-American, and 168 men from each group had a prostate cancer diagnosis from their biopsy.
The researchers found that the mean 25-OH D levels were significantly lower among African-American men (16.7 ng/ml) compared with European-American men (19.3 ng/ml). The highest 25-OH D level was 71 ng/ml in European-American men, while it was only 45 ng/ml in African-American men.
They categorized the study group into those whose 25-OH D levels were less than 12 ng/ml, less than 16 ng/ml, less than 20 ng/ml, and less than 30 ng/ml, and found a dose-response relationship between tumor grade and vitamin D level for both European-American and African-American men, and the association held true even after adjusting for potential confounders including diet, smoking habits, obesity, family history, and calcium intake.
The researchers also found an association between lower 25-OH D levels and those at high and very high risk for prostate cancer, per National Comprehensive Cancer Network (NCCN) criteria, which take into account prediagnosis PSA levels, tumor stage, and Gleason grade.
While no association was found between vitamin D deficiency and prostate cancer diagnosis in European-American men, this association was significant in African-American men. Further, the association with disease aggressiveness and cancer spread was stronger for African-American men than for European-American men. Skin color, which determines cumulative vitamin D levels from exposure to sun, may partly explain the discrepancies observed between European-American and African-American men, explained Murphy.
"We will next evaluate genetic polymorphisms in the pathways of vitamin D metabolism to better understand the risk alleles underlying this association," said Murphy. "Vitamin D deficiency seems to be important for general wellness and may be involved in the formation or progression of several human cancers. It would be wise to be screened for vitamin D deficiency and treated."
Rick Kittles, Ph.D., an associate professor of medicine and epidemiology at the University of Illinois in Chicago, is a co-author and collaborator on this project.
This study was funded by the National Institutes of Health and the U.S. Department of Defense. Murphy and Kittles declare no conflicts of interest.
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