Circulating vitamin D concentration and risk of prostate cancer: a dose–response meta-analysis of prospective studies
Authors Gao JL, Wei W, Wang G, Zhou HL, Fu YW, Liu N
Received 16 August 2017
Accepted for publication 12 October 2017
Published 9 January 2018 Volume 2018:14 Pages 95—104
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Deyun Wang
Jialin Gao, Wei Wei, Gang Wang, Honglan Zhou, Yaowen Fu, Nian Liu
Department of Urology, The First Hospital of Jilin University, Changchun, People’s Republic of China
Background: Though many studies have been performed to elucidate the association between circulating vitamin D and prostate cancer, no conclusive result is available. We carried out a dose–response meta-analysis to quantitatively examine the association of circulating 25-hydroxyvitamin D (25[OH]D) concentration with prostate cancer.
Methods: Only prospective studies examining the associations of circulating 25[OH]D concentration with prostate cancer were eligible for the meta-analysis. A random-effect meta-analysis was done first, to calculate the summary relative risk (RR) and 95% confidence intervals (CIs) comparing the higher concentration with the lower concentration of 25[OH]D. A dose–response meta-analysis using random-effects model was then carried out to evaluate the nonlinearity and calculate the summary RR caused per 10 ng/mL increment.
Results: Nineteen prospective cohort or nested case–control studies were included. Higher 25[OH]D concentration was significantly correlated with elevated risk of prostate cancer (RR =1.15, 95% CI 1.06–1.24). No nonlinear relationship was found between 25[OH]D concentration and risk of prostate cancer (P=0.654). Dose–response meta-analysis showed that the summary RR caused per 10 ng/mL increment in circulating 25[OH]D concentration was 1.04 (95% CI 1.02–1.06). Subgroup analysis also found a modest dose–response relationship. Funnel plot and Egger’s test did not detect publication bias.
Conclusion: The findings suggest that highest 25[OH]D concentration is correlated with elevated risk of prostate cancer and a modest dose–response effect exists in this association; however, more studies are needed.
Keywords: vitamin D, prostate cancer, dose–response meta-analysis
Prostate cancer is the most common malignancy among men worldwide.1 In addition, the incidence of prostate cancer has increased significantly in most Asian populations.2 There has been a lot of progress in the therapeutic options including novel molecularly targeted therapeutics for prostate cancer patients in the past decade.3,4 Over the past decade, many clinical or experimental studies have provided many fundamental insights into the pathogenesis of prostate cancer.5–7 There are a number of risk factors for prostate cancer reported in published literatures, such as vasectomy and alcohol intake.8–10 However, there is still limited number of modifiable risk factors identified for prostate cancer and more studies are needed to identify some modifiable risk factors associated with prostate cancer.
The roles of vitamin D in human diseases have received increased attention, and it has been regarded as a vital hormone to maintain the normal functions of various organs or systems in the bodies.11–14 Vitamin D has some extraskeletal biological functions including inhibiting the progression of cancer cells.15,16 A previous study has found that vitamin D can exert a key role in decreasing cancer risk.17 Meta-analyses of epidemiological studies have suggested that higher circulating 25-hydroxyvitamin D (25[OH]D) concentration is correlated with decreased risks of several common cancers, such as colorectal cancer and bladder cancer.18,19 Considering the preventive effect of vitamin D against cancer, many researchers also studied the association of circulating 25[OH]D concentration with prostate cancer.20–28 Some studies reported that higher serum 25[OH]D concentration modestly increased the risk of prostate cancer.26,29,30 However, other studies did not find any correlation of vitamin D with prostate cancer.25,27–29 These studies have obtained controversial results on the impact of circulating 25[OH]D on prostate cancer risk, and no conclusive result is available. Thus, we carried out a comprehensive literature search and performed a meta-analysis to examine the association of circulating 25[OH]D concentration with prostate cancer.
Search strategy and inclusion criteria
PubMed and Web of Science were searched for prospective studies, examining the correlation of circulating 25[OH]D concentration with prostate cancer, which were eligible for the meta-analysis. We carried out the literature search on December 20, 2016. We used combinations of the following keywords: (“vitamin D” or “25-hydroxyvitamin D” or “25[OH]D”) AND (“prostate cancer” or “prostate carcinoma”). The references from included articles were also checked to identify any additional studies.
Only prospective cohort studies or nested case–control studies examining the associations of circulating 25[OH]D concentration with prostate cancer and reporting relative risks (RRs) of prostate cancer across at least three categories of circulating 25[OH]D levels were eligible for the meta-analysis. Case–control studies, cross-sectional studies, and retrospective cohort studies were excluded. Studies without RRs of prostate cancer across at least three categories of 25[OH]D concentrations were also excluded. Studies containing overlapping data were also excluded.
Data extraction and quality assessment
Two investigators extracted data independently, and any disagreement was resolved by consensus among all investigators. For each study, we extracted RRs of prostate cancer comparing the upper categories of circulating 25[OH]D concentration with the lowest category of circulating 25[OH]D level. For the dose–response meta-analysis, the number of cases and noncases, concentration level, and adjusted RR for each category and its 95% confidence interval (CI) were extracted. For the studies that did not provide the median or mean levels of serum 25[OH]D, we used the midpoint of each category as the alternative. For the open-ended category, the midpoint of this category was calculated by assuming that the interval was the same as that of the adjacent category. When the numbers of cases/noncases in each category were not available, the numbers were estimated by the methods proposed by Aune et al.31 For studies that did not set the lowest category as reference, we used the method described by Hamling et al32 to make a transformation. Furthermore, we gathered information on study design, country, sample size, matching factors, and time of follow-up or from blood collection to diagnosis. Studies with >300 prostate cancer cases were defined as studies with large sample size, while those with <300 prostate cancer cases were defined as studies with small sample size. The quality assessment was done by the recommendation from Newcastle–Ottawa Scale (NOS), which encompassed three perspectives including selection of participants, comparability, and outcome assessment, and studies scoring at least 6 stars were classified as high-quality studies.33
The homogeneity among those included studies was estimated by the I2 statistic, and I2>50% represented high concentration of heterogeneity.34 A random-effect meta-analysis was first done to calculate the summary RR and 95% CI comparing the higher concentration with the lower concentration of 25[OH]D.35 The dose–response meta-analysis was performed using the method proposed by Greenland and Longnecker36 and Orsini et al.37 In order to explore the nonlinear dose–response curve, serum 25[OH]D concentrations were modeled using restricted cubic splines with three knots at fixed percentiles (0.10, 0.50, and 0.90) of the distribution. The P-value of nonlinearity was calculated by testing against the null hypothesis that the coefficient of the second spline was equal to 0. If the nonlinearity was not statistically significant, the linear dose–response outcomes were presented per 10 ng/mL (25 nmol/L) increment in serum 25[OH]D by random-effects model.35–37
Subgroup analysis was performed by sample size, publication year, study designs, and adjustment for calcium intake. Sensitivity analysis was carried out by excluding any single study by turns. Publication bias was evaluated by funnel plot and the Egger test.38 The traditional meta-analysis was carried out using STATA (Version 12.0), and the dose–response meta-analysis was performed by R and its dosresmeta package.39
Characteristics of included studies
The study selection process is shown in Figure 1. Though >1,530 articles were found, only 42 studies were possibly eligible and evaluated by checking the full texts.16,20–30,40–69 Twenty-three studies were then excluded,16,40–61 and the remaining 19 studies were considered eligible.20–30,62–69 There were three prospective cohort studies and 16 nested case–control studies (Table 1). Most studies were carried out in Europe and USA except one study from Japan (Table 1). The number of prostate cancer cases in those 19 studies varied obviously and ranged from 61 to 2,106 (Table 1). A total of 12,786 prostate cancer cases and 35,583 participants were included in those 19 studies. There were seven studies with <300 prostate cancer cases and 12 studies with >300 prostate cancer cases (Table 1). All 19 studies reported the adjusted RRs of prostate cancer across at least three categories of circulating 25[OH]D levels. According to the NOS criteria, all included studied scored >6 stars and thus had high quality.
Figure 1 Selection of studies for inclusion in meta-analysis.
When performing meta-analysis of RRs comparing the higher concentration with the lower concentration of 25[OH]D, there was good homogeneity among those included studies (I2=0%). Higher 25[OH]D concentration was significantly correlated with elevated risk of prostate cancer (RR =1.15, 95% CI 1.06–1.24, P=0.001) (Figure 2). The summary RR was not significantly changed in the sensitivity analysis. As shown in Table 2, in the subgroup analysis of studies with small sample size, with cohort study design, there was no significant correlation of circulating 25[OH]D concentration with prostate cancer. The adjustment for calcium supplementation did not change the positive association between the serum 25[OH]D and risk of prostate cancer.
Figure 2 Higher 25[OH]D concentration was significantly correlated with elevated risk of prostate cancer.
Table 2 The results of subgroup analysis between 25[OH]D concentration and risk of prostate cancer
For the dose–response meta-analysis, as shown in Figure 3, there was no nonlinear relationship between circulating 25[OH]D concentration and the risk of prostate cancer (P=0.654). When performing meta-analysis of RRs of prostate cancer risk caused by per 10 ng/mL increment in circulating 25[OH]D level, there was also good homogeneity among those included studies (I2=0%). Linear dose–response meta-analysis showed the summary RR caused by per 10 ng/mL increment in circulating 25[OH]D concentration was 1.04 (95% CI 1.02–1.06, P<0.001) (Figure 4). The summary RR was not significantly changed in the sensitivity analysis. As shown in Table 2, subgroup analysis using data from studies of large sample size also found a modest dose–response relationship (RR =1.04, 95% CI 1.02–1.06, P<0.001). However, subgroup analysis using data from studies of small sample size or cohort study design did not find an obvious dose–response relationship (Table 2).
Figure 3 Nonlinear dose–response relationship between 25[OH]D concentration and risk of prostate cancer.
Figure 4 Linear dose–response relationship between circulating 25[OH]D concentration and prostate cancer.
The funnel plot did not detect publication bias (Figure 5). Besides, the P-value of Egger test was 0.48 and provided another evidence for the lack of publication bias.
Figure 5 The funnel plot in the dose–response meta-analysis did not detect publication bias.
Though the preventive roles of vitamin D have been found in several cancers, its role in the development of prostate cancer is still unclear. Those published studies did not report consistent findings. We therefore carried out a dose–response meta-analysis to quantitatively elucidate the impact of circulating 25[OH]D concentration on prostate cancer. A total of 19 prospective studies were finally eligible for the meta-analysis. We found that higher 25[OH]D concentration was significantly correlated with elevated risk of prostate cancer (RR =1.15, P=0.001; Figure 1). Dose–response meta-analysis showed the summary RR of prostate cancer caused by per 10 ng/mL increment was 1.04 (P<0.001; Figure 2). Therefore, the findings from the meta-analysis suggested that higher 25[OH]D concentration was correlated with elevated risk of prostate cancer and a modest dose–response effect existed in this association.
In human bodies, vitamin D is mainly synthesized in the skin after exposure to solar UV radiation and vitamin D can also be ingested from some foods.70,71 25[OH]D is the hydroxylated form of vitamin D, which is the mostly used biomarker of circulating vitamin D and widely used in clinical practice.72 A large number of published studies have found that vitamin D can exert a key role in decreasing cancer risk.17–19,73–75 The antitumor effects of vitamin D have been well established in several cancers, such as colorectal cancer and bladder cancer.18,19 On the contrary, some studies found that vitamin D did not exert an antitumor effect in prostate cancer but even caused elevated risk of prostate cancer.26,29,30 This present meta-analysis of 19 prospective studies provided epidemiological evidence for the tumor-promoting effect of vitamin D in prostate cancer though the effect was modest. However, no clear biological relationship has been found between high levels of vitamin D and an increased risk of prostate cancer. We can only speculate on the cause for the tumor-promoting effect of vitamin D in prostate cancer.25 One reason might be that 25[OH]D may be a marker of other factors that related to the risk of prostate cancer. For example, insulin-like growth factor-I (IGF-I) has been related to prostate cancer76–78 and a relationship between 25[OH]D and insulin-like growth factor-1 has been reported.79 Moreover, higher 25[OH]D might be associated with an increased detection rate of prostate cancer.25 However, we cannot rule out this detection bias using the summary outcome from the included studies in our research. The findings in the meta-analysis may have important indications from the supplementation of vitamin D in men. The use of vitamin D in men with high risk of prostate cancer may be cautious considering the tumor-promoting effect of vitamin D in prostate cancer.
A major strength of this meta-analysis was the inclusion of a total of 19 prospective cohort studies or nested case–control studies. The large number of participants in the meta-analysis could help us quantitatively examine the association of circulating 25[OH]D concentration with prostate cancer and get a more credible finding. As shown in Table 1, all included studies used a prospective design and reported adjusted RRs of prostate cancer, which ensured the appropriate selection of participants, the correct assessment of outcomes. In addition, there were 12 studies with >300 prostate cancer cases, which could increase the statistical power and decrease the risk of possible bias caused by small sample size (Table 1). Another strength of this meta-analysis was the good homogeneity among those included studies (I2=0%), which suggested the lack of obvious heterogeneity in the meta-analysis. There was good homogeneity in both the meta-analysis of RRs comparing the higher concentration with the lower concentration of 25[OH]D and the meta-analysis of RRs of prostate cancer risk caused by per 10 ng/mL increment. There is no doubt that the homogeneity could strengthen the evidence for the tumor-promoting effect of vitamin D in prostate cancer found in the meta-analysis.
There were several limitations and the outcomes should be interpreted cautiously. First, some included studies did not consider the influence of other factors, such as vitamin D intake and sun exposure, on the association between circulating 25[OH]D concentration and prostate cancer, which might cause possible risk of bias. Therefore, more studies taking into account those factors are needed to provide a more definite assessment of the influence of circulating 25[OH]D concentration on prostate cancer risk. Second, the reagents used to detect circulating 25[OH]D concentration were various across those included studies, which could cause possible heterogeneity in the meta-analysis. However, there was good homogeneity among those included studies (I2=0%), which proved the little influence of different reagents used to detect circulating 25[OH]D concentration in the meta-analysis. Third, because all the included studies were done in developed countries and most studies were done in the Western countries (northern Europe and USA), the findings could not be generalized to other countries from different ethnicities. There was only one study with small sample size from Asian countries.28 Participants in the studies that conducted in the USA were mostly white, and only one study with moderate sample size had multiple ethnics.65 Therefore, more studies assessing the correlation of vitamin D with prostate cancer risk from other ethnicities and developing countries are needed. Finally, results of subgroups were based on a limited number of studies and we cannot rule out the possibility that insufficient statistical power may be present.
The findings from the meta-analysis suggest that higher 25[OH]D concentration is correlated with elevated risk of prostate cancer and a modest dose–response effect exists. Besides, these results need to be validated in further studies. The biological explanation for the positive correlation of vitamin D with prostate cancer risk is unclear, and further research is needed to address this issue.
The authors report no conflicts of interest in this work.
Attard G, Parker C, Eeles RA, et al. Prostate cancer. Lancet. 2016;387(10013):70–82.
Ito K. Prostate cancer in Asian men. Nat Rev Urol. 2014;11(4):197–212.
Ritch CR, Cookson MS. Advances in the management of castration resistant prostate cancer. BMJ. 2016;355:i4405.
Yap TA, Smith AD, Ferraldeschi R, Al-Lazikani B, Workman P, de Bono JS. Drug discovery in advanced prostate cancer: translating biology into therapy. Nat Rev Drug Discov. 2016;15(10):699–718.
Spratt DE, Zumsteg ZS, Feng FY, Tomlins SA. Translational and clinical implications of the genetic landscape of prostate cancer. Nat Rev Clin Oncol. 2016;13(10):597–610.
Lee JK, Phillips JW, Smith BA, et al. N-Myc drives neuroendocrine prostate cancer initiated from human prostate epithelial cells. Cancer Cell. 2016;29(4):536–547.
Cancer Genome Atlas Research Network. The molecular taxonomy of primary prostate cancer. Cell. 2015;163(4):1011–1025.
Zhao J, Stockwell T, Roemer A, Chikritzhs T. Is alcohol consumption a risk factor for prostate cancer? A systematic review and meta-analysis. BMC Cancer. 2016;16(1):845.
Kelly SP, Graubard BI, Andreotti G, Younes N, Cleary SD, Cook MB. Prediagnostic body mass index trajectories in relation to prostate cancer incidence and mortality in the PLCO cancer screening trial. J Natl Cancer Inst. 2017;109(3):djw225.
Nayan M, Hamilton RJ, Macdonald EM, et al; Canadian Drug Safety and Effectiveness Research Network (CDSERN). Vasectomy and risk of prostate cancer: population based matched cohort study. BMJ. 2016;355:i5546.
Reynolds J, Ray D, Alexander MY, Bruce I. Role of vitamin D in endothelial function and endothelial repair in clinically stable systemic lupus erythematosus. Lancet. 2015;385(suppl 1):S83.
Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 2016;96(1):365–408.
Langer J, Penna-Martinez M, Bon D, Herrmann E, Wallasch M, Badenhoop K. Insufficient vitamin D response to solar radiation in German patients with type 2 diabetes or gestational diabetes. Horm Metab Res. 2016;48(8):503–508.
Maia-Ceciliano TC, Barreto-Vianna AR, Barbosa-da-Silva S, Aguila MB, Faria TS, Mandarim-de-Lacerda CA. Maternal vitamin D-restricted diet has consequences in the formation of pancreatic islet/insulin-signaling in the adult offspring of mice. Endocrine. 2016;54(1):60–69.
Kelly JL, Salles G, Goldman B, et al. Low serum vitamin D levels are associated with inferior survival in follicular lymphoma: a prospective evaluation in SWOG and LYSA studies. J Clin Oncol. 2015;33(13):1482–1490.
Nyame YA, Murphy AB, Bowen DK, et al. Associations between serum vitamin D and adverse pathology in men undergoing radical prostatectomy. J Clin Oncol. 2016;34(12):1345–1349.
Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014;14(5):342–357.
Garland CF, Gorham ED. Dose–response of serum 25-hydroxyvitamin D in association with risk of colorectal cancer: a meta-analysis. J Steroid Biochem Mol Biol. 2016;168:1–8.
Zhao Y, Chen C, Pan W, et al. Comparative efficacy of vitamin D status in reducing the risk of bladder cancer: a systematic review and network meta-analysis. Nutrition. 2016;32(5):515–523.
Braun MM, Helzlsouer KJ, Hollis BW, Comstock GW. Prostate cancer and prediagnostic levels of serum vitamin D metabolites (Maryland, United States). Cancer Causes Control. 1995;6(3):235–239.
Nomura AM, Stemmermann GN, Lee J, et al. Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States). Cancer Causes Control. 1998;9(4):425–432.
Baron JA, Beach M, Wallace K, et al. Risk of prostate cancer in a randomized clinical trial of calcium supplementation. Cancer Epidemiol Biomarkers Prev. 2005;14(3):586–589.
Barnett CM, Nielson CM, Shannon J, et al. Serum 25-OH vitamin D levels and risk of developing prostate cancer in older men. Cancer Causes Control. 2010;21(8):1297–1303.
Brandstedt J, Almquist M, Manjer J, Malm J. Vitamin D, PTH, and calcium and the risk of prostate cancer: a prospective nested case–control study. Cancer Causes Control. 2012;23(8):1377–1385.
Meyer HE, Robsahm TE, Bjorge T, Brustad M, Blomhoff R. Vitamin D, season, and risk of prostate cancer: a nested case–control study within Norwegian health studies. Am J Clin Nutr. 2013;97(1):147–154.
Kristal AR, Till C, Song X, et al. Plasma vitamin D and prostate cancer risk: results from the selenium and vitamin E cancer prevention trial. Cancer Epidemiol Biomarkers Prev. 2014;23(8):1494–1504.
Skaaby T, Husemoen LL, Thuesen BH, et al. Prospective population-based study of the association between serum 25-hydroxyvitamin-D levels and the incidence of specific types of cancer. Cancer Epidemiol Biomarkers Prev. 2014;23(7):1220–1229.
Sawada N, Inoue M, Iwasaki M, et al. Plasma 25-hydroxy vitamin D and subsequent prostate cancer risk in a nested case–control study in Japan: the JPHC study. Eur J Clin Nutr. 2017;71(1):132–136.
Schenk JM, Till CA, Tangen CM, et al. Serum 25-hydroxyvitamin D concentrations and risk of prostate cancer: results from the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev. 2014;23(8):1484–1493.
Albanes D, Mondul AM, Yu K, et al. Serum 25-hydroxy vitamin D and prostate cancer risk in a large nested case–control study. Cancer Epidemiol Biomarkers Prev. 2011;20(9):1850–1860.
Aune D, Greenwood DC, Chan DS, et al. Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose–response meta-analysis of prospective studies. Ann Oncol. 2012;23(4):843–852.
Hamling J, Lee P, Weitkunat R, Ambuhl M. Facilitating meta-analyses by deriving relative effect and precision estimates for alternative comparisons from a set of estimates presented by exposure level or disease category. Stat Med. 2008;27(7):954–970.
Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. 2015. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed September 28, 2017.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–560.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–188.
Greenland S, Longnecker MP. Methods for trend estimation from summarized dose–response data, with applications to meta-analysis. Am J Epidemiol. 1992;135(11):1301–1309.
Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D. Meta-analysis for linear and nonlinear dose–response relations: examples, an evaluation of approximations, and software. Am J Epidemiol. 2012;175(1):66–73.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–634.
Crippa A, Orsini N. Multivariate dose–response meta-analysis: the dosresmeta R package. J Stat Softw. 2016;72(Code Snippet 1):15.
Atoum MF, AlKateeb D, AlHaj Mahmoud SA. The Fok1 vitamin D receptor gene polymorphism and 25(OH) D serum levels and prostate cancer among Jordanian men. Asian Pac J Cancer Prev. 2015;16(6):2227–2230.
Choo CS, Mamedov A, Chung M, Choo R, Kiss A, Danjoux C. Vitamin D insufficiency is common in patients with nonmetastatic prostate cancer. Nutr Res. 2011;31(1):21–26.
Fang F, Kasperzyk JL, Shui I, et al. Prediagnostic plasma vitamin D metabolites and mortality among patients with prostate cancer. PLoS One. 2011;6(4):e18625.
Galunska B, Gerova D, Kosev P, Anakievski D, Hinev A. Serum 25-hydroxy vitamin D levels in Bulgarian patients with prostate cancer: a pilot study. Clin Lab. 2015;61(3–4):329–335.
Gilbert R, Martin RM, Fraser WD, et al. Predictors of 25-hydroxyvitamin D and its association with risk factors for prostate cancer: evidence from the prostate testing for cancer and treatment study. Cancer Causes Control. 2012;23(4):575–588.
Gilbert R, Metcalfe C, Fraser WD, et al. Associations of circulating 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and vitamin D pathway genes with prostate-specific antigen progression in men with localized prostate cancer undergoing active monitoring. Eur J Cancer Prev. 2013;22(2):121–125.
Grant WB. A multicountry ecologic study of risk and risk reduction factors for prostate cancer mortality. Eur Urol. 2004;45(3):271–279.
Grant WB. The roles of ultraviolet-B irradiance, vitamin D, apolipoprotein E epsilon4, and diet in the risk of prostate cancer. Cancer Causes Control. 2011;22(1):157–158.
Hendrickson WK, Flavin R, Kasperzyk JL, et al. Vitamin D receptor protein expression in tumor tissue and prostate cancer progression. J Clin Oncol. 2011;29(17):2378–2385.
Jackson MD, Tulloch-Reid MK, Lindsay CM, et al. Both serum 25-hydroxyvitamin D and calcium levels may increase the risk of incident prostate cancer in Caribbean men of African ancestry. Cancer Med. 2015;4(6):925–935.
John EM, Schwartz GG, Koo J, Van Den Berg D, Ingles SA. Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer. Cancer Res. 2005;65(12):5470–5479.
Murphy AB, Nyame Y, Martin IK, et al. Vitamin D deficiency predicts prostate biopsy outcomes. Clin Cancer Res. 2014;20(9):2289–2299.
Nelson SM, Batai K, Ahaghotu C, Agurs-Collins T, Kittles RA. Association between serum 25-hydroxy-vitamin D and aggressive prostate cancer in African American men. Nutrients. 2016;9(1):12.
Paller CJ, Kanaan YM, Beyene DA, et al. Risk of prostate cancer in African-American men: evidence of mixed effects of dietary quercetin by serum vitamin D status. Prostate. 2015;75(13):1376–1383.
Pazdiora P, Svobodova S, Fuchsova R, et al. Vitamin D in colorectal, breast, prostate and lung cancer: a pilot study. Anticancer Res. 2011;31(10):3619–3621.
Roca E, Valcamonico F, Amoroso V, et al. Serum vitamin D and prostate cancer prognosis: the story continues. J Clin Oncol. 2016;34(30):3709–3710.
Schwartz GG. Vitamin D in blood and risk of prostate cancer: lessons from the selenium and vitamin E cancer prevention trial and the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev. 2014;23(8):1447–1449.
Steck SE, Arab L, Zhang H, et al. Association between plasma 25-hydroxyvitamin D, ancestry and aggressive prostate cancer among African Americans and European Americans in PCaP. PLoS One. 2015;10(4):e0125151.
Stephan C, Lein M, Matalon J, et al. Serum vitamin D is not helpful for predicting prostate cancer aggressiveness compared with the prostate health index. J Urol. 2016;196(3):709–714.
Trump DL, Chadha MK, Sunga AY, et al. Vitamin D deficiency and insufficiency among patients with prostate cancer. BJU Int. 2009;104(7):909–914.
Tseng M, Breslow RA, Graubard BI, Ziegler RG. Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. Am J Clin Nutr. 2005;81(5):1147–1154.
Yaturu S, Zdunek S, Youngberg B. Vitamin D levels in subjects with prostate cancer compared to age-matched controls. Prostate Cancer. 2012;2012:524206.
Ahn J, Peters U, Albanes D, et al; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Project Team. Serum vitamin D concentration and prostate cancer risk: a nested case–control study. J Natl Cancer Inst. 2008;100(11):796–804.
Faupel-Badger JM, Diaw L, Albanes D, Virtamo J, Woodson K, Tangrea JA. Lack of association between serum levels of 25-hydroxyvitamin D and the subsequent risk of prostate cancer in Finnish men. Cancer Epidemiol Biomarkers Prev. 2007;16(12):2784–2786.
Jacobs ET, Giuliano AR, Martinez ME, Hollis BW, Reid ME, Marshall JR. Plasma levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and the risk of prostate cancer. J Steroid Biochem Mol Biol. 2004;89–90(1–5):533–537.
Park SY, Cooney RV, Wilkens LR, Murphy SP, Henderson BE, Kolonel LN. Plasma 25-hydroxyvitamin D and prostate cancer risk: the multiethnic cohort. Eur J Cancer. 2010;46(5):932–936.
Platz EA, Leitzmann MF, Hollis BW, Willett WC, Giovannucci E. Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer. Cancer Causes Control. 2004;15(3):255–265.
Shui IM, Mucci LA, Kraft P, et al. Vitamin D-related genetic variation, plasma vitamin D, and risk of lethal prostate cancer: a prospective nested case–control study. J Natl Cancer Inst. 2012;104(9):690–699.
Travis RC, Crowe FL, Allen NE, et al. Serum vitamin D and risk of prostate cancer in a case–control analysis nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Am J Epidemiol. 2009;169(10):1223–1232.
Tuohimaa P, Tenkanen L, Ahonen M, 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(1):104–108.
Bandera Merchan B, Morcillo S, Martin-Nunez G, Tinahones FJ, Macias-Gonzalez M. The role of vitamin D and VDR in carcinogenesis: through epidemiology and basic sciences. J Steroid Biochem Mol Biol. 2016;167:203–218.
Trummer C, Pandis M, Verheyen N, et al. Beneficial effects of UV-radiation: vitamin D and beyond. Int J Environ Res Public Health. 2016;13(10):1028.
Batai K, Murphy AB, Nonn L, Kittles RA. Vitamin D and immune response: implications for prostate cancer in African Americans. Front Immunol. 2016;7:53.
Iniesta RR, Paciarotti I, Davidson I, et al. 5-Hydroxyvitamin D concentration in paediatric cancer patients from Scotland: a prospective cohort study. Br J Nutr. 2016;116(11):1926–1934.
Shan NL, Wahler J, Lee HJ, et al. Vitamin D compounds inhibit cancer stem-like cells and induce differentiation in triple negative breast cancer. J Steroid Biochem Mol Biol. 2016;173:122–129.
Luan Z, Ma Y, Xin Y, Qian J, Wang H. Possible molecular mechanisms by which vitamin D prevents inflammatory bowel disease and colitis-associated colorectal cancer. Curr Med Chem. 2016;24(9):911–917.
Chan JM, Stampfer MJ, Giovannucci E, et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science. 1998;279(5350):563–566.
Chan JM, Stampfer MJ, Ma J, et al. Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer. J Natl Cancer Inst. 2002;94(14):1099–1106.
Stattin P, Bylund A, Rinaldi S, et al. Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study. J Natl Cancer Inst. 2000;92(23):1910–1917.
Hypponen E, Boucher BJ, Berry DJ, Power C. 25-hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: a cross-sectional study in the 1958 British Birth Cohort. Diabetes. 2008;57(2):298–305.
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF]