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Vitamin D Level and Prognosis in Patients with Prostate Cancer
Abstract & commentary
By William B. Ershler, MD
Synopsis: Calcidiol (25(OH)D) levels were measured in a series of 160 Norwegian prostate cancer patients, and the results correlated with cancer-specific and all-cause mortality. Compared to those with low levels, patients with medium or high levels experienced less cancer-specific mortality, and this was particularly notable in those who received some form of hormonal treatment.
Source: Tretli S, et al. Association between serum 25(OH)D and death from prostate cancer. Br J Cancer. 2009;100: 450-454.
It has long been held that there is a relationship between insufficient sun exposure and cancer death.1,2 Indeed, the mortality rates for breast, prostate, lung, skin, and lymphoma have each been shown to vary in accordance with sun exposure. Experimental studies have demonstrated an effect of vitamin D on key cell-cycle processes, including proliferation and apoptosis,3 and it has been proposed that vitamin D influences cancer progression.
Vitamin D levels are dependent on a number of factors, including sunlight. The most active form, calcitriol (1,25(OH)2D), is produced in the kidney from calcidiol (25(OH)D). The amount of vitamin D in the body is closely associated with the concentration of calcidiol in the blood.
The current report is from Norway where, during winter months, typical exposure to sunlight is very low, and this is reflected by low blood levels of 25(OH)D in the general population during these months. Curiously, Tretli et al have discovered that patients who were diagnosed with cancer of the breast, colon, prostate, lung, or lymphoma during the summer or autumn were found to have better prognosis (15%-50%) than patients diagnosed during winter months.4,5 To more directly relate these observations to vitamin D sufficiency, pretreatment 25(OH)D levels were determined in prostate cancer patients and associated with clinical outcome. The study capitalized on an outstanding national registry and serum bank (the Janus serum bank, established in 1973). A total of 160 patients with prostate cancer were included in the analysis. Of these, 37 had received hormone therapy for a median of 2.4 years prior to the vitamin D blood sampling, and this cohort (Group 1) was considered separately from the remaining 123 patients who had vitamin D levels determined at the time of diagnosis and prior to therapy. All patients received some form of therapy for their prostate cancer, including radiation, surgery, and/or hormonal therapy. In total, 97 of the 160 patients received hormone therapy, most frequently with leutinizing hormone-releasing hormone (LHRH) or orchiectomy. Additional variables, including patient age, ECOG performance status, and tumor grade were factored into the analysis.
The serum level of 25(OH)D was classified as low (< 50 nmol/L), medium (50-80 nmol/L), or high (> 80 nmol /L). A Cox proportional hazard regression model was used to assess the association between serum 25(OH)D and cancer mortality. During follow-up, 61 deaths occurred, of whom 52 died of prostate cancer. The median time of follow-up was 44.0 months (range, 1.2-154.6). Serum 25(OH)D at medium or high levels were significantly related to better prognosis (RR 0.33; 95% CI 0.14-0.77, RR 0.16; 95% CI 0.05-0.43), compared with the low level. Analysis restricted to those 97 patients receiving hormone therapy gave a stronger association (RR 0.18, 95% CI 0.07-0.46 and RR 0.09, 95 % CI 0.03-0.27, respectively, for those with medium or high 25(OH)D levels, compared to those with low levels.
Thus, there was a clear association of serum 25(OH)D level and cause-specific mortality in prostate cancer. Although it is doubtful that such is unique to Norway, perhaps it is likely to be most demonstrable in such a northern environment where sunlight exposure varies strikingly in a seasonal manner. Nonetheless, in this series of 160 patients, the association was quite strong. Yet, as Trietl et al point out, association studies do not set out to prove causality, and the findings should not be extrapolated to indicate vitamin D replacement in prostate cancer treatment strategies in anything but a controlled clinical trial.
Whereas there are mechanisms postulated to account for the protective effect of vitamin D, there are also reports that high levels of this vitamin may be associated with an increased risk for prostate cancer development6 or more aggressive disease.7 It is quite clear that there is a lot we don't know about vitamin D and cancer in general. Certainly, the data presented would indicate that serum levels might prove to be useful in prognosis. Whether supplementation for those with low levels will be useful in prevention or treatment should be the subject of well-constructed clinical trials.
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2. John EM, et al. Vitamin D and breast cancer risk: the NHANES I Epidemiologic follow-up study, 1971-1975 to 1992. National Health and Nutrition Examination Survey. Cancer Epidemiol Biomarkers Prev. 1999;8: 399-406.
3. Holick MF. Vitamin D: its role in cancer prevention and treatment. Prog Biophys Mol Biol. 2006;92: 49-59.
4. Porojnicu AC, et al. Seasonal and geographical variations in lung cancer prognosis in Norway. Does Vitamin D from the sun play a role? Lung Cancer. 2007;55: 263-270.
5. Porojnicu AC, et al. Season of diagnosis is a prognostic factor in Hodgkin's lymphoma: a possible role of sun-induced vitamin D. Br J Cancer. 2005;93: 571-574.
6. Tuohimaa P, et al. Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Int J Cancer. 2004;108: 104-108.
7. Ahn J, et al. Serum vitamin D concentration and prostate cancer risk: a nested case-control study. J Natl Cancer Inst. 2008;100: 796-804.