Published: May 2, 2014 | Updated: May 5, 2014
By Charles Bankhead, Staff Writer, MedPage Today

Action Points

• In African-American men, vitamin D deficiency was associated with increased odds of prostate cancer diagnosis on biopsy.
• In both European-American and African-American men, severe vitamin D deficiency was positively associated with higher Gleason grade and tumor stage.

Vitamin D deficiency had a significant association with aggressive tumor characteristics in men with newly diagnosed prostate cancer, a study of 667 men showed.

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A 25-hydroxyvitamin D (25-OH D) <12 ng/mL more than tripled the likelihood that the biopsy would reveal a high Gleason score and doubled the odds for a higher disease stage.

Among African-American men, low serum 25-OH D also increased the odds of prostate cancer diagnosis, Adam B. Murphy, MD, of Northwestern University, and co-authors reported in Clinical Cancer Research.

“If vitamin D is involved in prostate cancer initiation or progression it would provide a modifiable risk factor for primary prevention and secondary prevention to progression, especially in the highest risk group of African-American men,” the authors noted in their discussion of the findings. “Vitamin D analogs could be useful agents to use in men on active surveillance to delay treatment.

“Therefore, there is a critical need for large epidemiologic studies that investigate the biologic and environment mediators of serum vitamin D and prostate cancer progression that include men of African ancestry.”

Despite advances in diagnosis and treatment of prostate cancer, substantial racial disparities persist in terms of incidence and mortality. As compared with their European-American counterparts, African-American men have a 60% greater risk of developing prostate cancer and more than a twofold greater risk of dying of the disease.

National health priorities include identifying causes of the disparities in prostate cancer incidence and mortality. Studies have shown that vitamin D deficiency has a higher prevalence in northern latitudes, older people, and African Americans.

Recently, studies have provided evidence for an inverse association between residential ultraviolet (UV) B radiation and several types of cancer in blacks, the authors continued. Some evidence also has suggested an inverse association between prostate cancer and UV radiation exposure in the U.S.

Data specifically linking vitamin D levels to prostate cancer have been suggestive but indirect. To inform possible associations between vitamin D and prostate cancer, Murphy and colleagues studied vitamin D status in men who underwent prostate biopsy as a result of elevated PSA levels or abnormal digital rectal exam. That population is less likely to differ significantly in screening practices, they reasoned.

“To our knowledge, there have been no studies evaluating the association of vitamin D and the outcomes of prostate biopsies,” the authors said. “We also evaluate these outcomes in an ethnically diverse population of ambulatory men in a city with low UV exposures.”

The study involved 667 men 40 to 79 who underwent a first prostate biopsy at five Chicago clinics because of elevated serum PSA level or abnormal digital rectal exam. Only ambulatory, nonhospitalized patients were recruited for the study. Serum 25-OH D was assessed on the basis of a blood sample drawn the day of enrollment.

Biopsy results revealed cancer in 383 men. As compared with the biopsy-negative group, men with prostate cancer were slightly older (62 versus 61, P=0.03), had a smaller prostate volume (42.9 versus 56.5 cm³, P<0.001), were more likely to have a family history of prostate cancer (25.8% versus 14.9%, P=0.001), and had less racial/ethnic diversity (14.4% versus 22.5% other than Caucasian or African American, P=0.01).

Men with positive versus negative biopsies had a similar prevalence of obesity, as 23% to 24% in both groups had a body mass index <30, 21% to 22% BMI≥30, and 19% versus 25.5% BMI ≥35.

The two groups did not differ in the proportion of men who were vitamin D deficient, defined as 25-OH-D <20 ng/mL (43.7% cases versus 37.8% controls, P=0.17). The groups also did not differ in the proportion with 25-OH-D levels <30 ng/mL (78.1% in cases, 75.2% in the men with negative biopsies). Overall, 15.7% of the men had severe vitamin deficiency, defined as 25-OH-D <12 ng/mL. The highest 25-OH-D level was 71 ng/mL in European American men and 45 ng/mL in African Americans.

Stratification by race showed that African-American men with positive prostate biopsies had significantly lower mean 25-OH-D level (16.7 versus 19.3 ng/mL, P=0.04), where as non-African-American men did not (25.7 versus 25.6 ng/mL).

Among European-American men tested, the investigators found no associations between vitamin D status and prostate cancer diagnosis, performing analyses of quartiles, tertiles, and several cut points for deficiency. They did find an association between 25-OH-D level and Gleason grade on biopsy (≤3+3, 3+4, and ≥4+4). The analysis yielded a significant association between 25-OH-D <12 ng/mL and Gleason grade ≥4+4 (P=0.02).

Analysis of tumor stage and 25-OH-D showed that European-American men with 25-OH-D <12 ng/mL had more than a twofold likelihood of ≥stage T2b versus ≤stage T2a (OR 2.42,P=0.008). Men who were vitamin D deficient also were more likely to meet NCCN criteria for high risk and very high risk as opposed to low and intermediate risk (P=0.025).

The same analyses of African-American men showed a significant association between serum 25-OH-D <20 ng/mL and a positive prostate biopsy (OR 2.43, P=0.01). Additionally, vitamin D-deficient (<12 ng/mL) African-American men had significantly increased odds for:

• Gleason grade ≥4+3 — OR 4.20, P=0.006
• Gleason grade ≥4+4 — OR 4.89, P=0.006
• Higher stage ≥stage T2b versus ≤stage T2a — OR 4.22, P=0.003
• Higher clinical TNM stage — P=0.02

The results are intriguing but should be interpreted with caution, said Stephen Freedland, MD of Duke University.

“They looked at vitamin D in many different ways — high versus low using multiple definitions, tertiles, and quartiles,” Freedland told MedPage Today by email. “They only report for high versus low using one level, and that level is different in each different analysis they reported. Whenever you look at something multiple times, you are more likely to find something — whether that is ‘true’ or not.”

The literature is mixed regarding the association between low vitamin D levels and aggressive prostate cancer. If one were to accept that the association exists, the implication would be that raising vitamin D levels might reduce the risk of aggressive prostate cancer, he added. Raising vitamin D levels can be challenging, as UV exposure carries a risk of skin cancer. Because vitamin D is fat soluble, people do not absorb vitamin D in skim milk fortified with the vitamin.

“Bottom line — intriguing findings, but small numbers and multiple analyses, and with conflicting literature that means this is an interesting hypothesis-generating study that requires confirmation before we start recommending vitamin D for everyone to prevent aggressive prostate cancer,” said Freedland.

The one factor clearly associated with aggressive prostate cancer is obesity, which often is a consequence of excessive intake of simple sugars.

“Thus, the best advice remains avoid simple sugars, avoid obesity, and exercise,” said Freedland. “Good for the heart and the prostate.”