Prostate cancerVitamin D levels

A study in Finland found some support for a beneficial effect of vitamin D in reducing the risk of prostate cancer: “that vitamin D has a protective role against prostate cancer only before the andropause, when serum androgen concentrations are higher. The lowest 25(OH)D concentrations in the younger men were associated with more aggressive prostate cancer. Furthermore, the high 25(OH)D levels delayed the appearance of clinically verified prostate cancer by 1.8 years1.” 

However, a subsequent study from Finland, Norway and Sweden found a U-shaped relationship between serum 25(OH)D level and prostate cancer incidence rates over a 17-year follow-up period2. As another study from Finland found an inverse correlation between serum 25(OH)D level and incidence of non-Hodgkin’s lymphoma for follow-ups less than seven years, but a direct correlation for longer follow-up periods3, the finding for prostate cancer can be attributed to too long a follow-up period, with serum 25(OH)D levels losing prognostic value4.

Studies of PCa incidence with respect to prediagnostic serum 25-hydroxyvitamin D [25(OH)D] measured five-to-15 years prior do not find a beneficial effect. There are several reviews and meta-analyses of the observational data5674. They find that the RR for higher 25(OH)D levels is near 1.00 with uncertainties that include 1.00. This is in contrast to breast and colorectal cancer, for which there is a clear risk reduction at higher serum 25(OH)D levels7. A study from Hawaii published after the meta-analyses567 and review also failed to find a beneficial effect of higher serum 25(OH)D levels8.

The Physicians’ Health Study was used to: “examine the associations of prediagnostic plasma levels of 25(OH)D and 1,25(OH)2D, individually and jointly, with total and aggressive disease, and explored whether relations between vitamin D metabolites and PCa were modified by the functional VDR FokI polymorphism, using conditional logistic regression. Men whose levels for both 25(OH)D and 1,25(OH)2D were below (versus above) the median had a significantly increased risk of aggressive PCa [OR = 2.1 (1.2-3.4)], although the interaction between the two vitamin D metabolites was not statistically significant (pinteraction = 0.23). A significant interaction was found between circulating 25(OH)D levels and the VDR FokI genotype (pinteraction < 0.05). Compared with those with plasma 25(OH)D levels above the median and with the FokI FF or Ff genotype, men who had low 25(OH)D levels and the less functional FokI ff genotype had increased risks of total (OR = 1.9, 95% CI 1.1-3.3) and aggressive PCa (OR = 2.5, 95% CI 1.1-5.8). Among men with plasma 25(OH)D levels above the median, the ff genotype was no longer associated with risk. Conversely, among men with the ff genotype, high plasma 25(OH)D level (above versus below the median) was related to significant 60% approximately 70% lower risks of total and aggressive PCa”9

In a case-control study nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial: “no statistically significant trend in overall PCa risk was observed with increasing season-standardized serum 25(OH)D level. However, serum 25(OH)D concentrations greater than the lowest quintile (Q1) were associated with increased risk of aggressive (Gleason sum > or = 7 or clinical stage III or IV) disease (in a model adjusting for matching factors, study center, and history of diabetes, ORs for Q2 vs Q1 = 1.20, 95% CI = 0.80 to 1.81, for Q3 vs Q1 =1.96, 95% CI = 1.34 to 2.87, for Q4 vs Q1 = 1.61, 95% CI = 1.09 to 2.38, and for Q5 vs Q1 = 1.37, 95% CI = 0.92 to 2.05; P(trend) = .05). The rates of aggressive PCa for increasing quintiles of serum 25(OH)D were 406, 479, 780, 633, and 544 per 100 000 person-years. In exploratory analyses, these associations with aggressive disease were consistent across subgroups defined by age, family history of PCa, diabetes, body mass index, vigorous physical activity, calcium intake, study center, season of blood collection, and assay batch”10

The likely explanation for the discrepancy between ecological studies of early life solar UVB irradiance and serum 25(OH)D levels a few years prior to PCa incidence is that since PCa takes several decades to be detected or lead to death, early life UVB irradiance and vitamin D are more important than in later life.

Page last edited: 24 August 2011

References

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  2. Tuohimaa, P. Tenkanen, L. Ahonen, M. Lumme, S. Jellum, E. Hallmans, G. Stattin, P. Harvei, S. Hakulinen, T. Luostarinen, T. Dillner, J. Lehtinen, M. Hakama, M. 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 Jan 1; 108 (1): 104-8.
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  5. Gupta, D. Lammersfeld, C. A. Trukova, K. Lis, C. G. Vitamin D and prostate cancer risk: a review of the epidemiological literature. Prostate Cancer Prostatic Dis. 2009 Apr 7;
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  8. Park, S. Y. Cooney, R. V. Wilkens, L. R. Murphy, S. P. Henderson, B. E. Kolonel, L. N. Plasma 25-hydroxyvitamin D and prostate cancer risk: the multiethnic cohort. Eur J Cancer. 2010 Mar; 46 (5): 932-6.
  9. Li, H. Stampfer, M. J. Hollis, J. B. Mucci, L. A. Gaziano, J. M. Hunter, D. Giovannucci, E. L. Ma, J. A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med. 2007 Mar; 4 (3): e103.
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