Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin D receptor (VDR), and VDR-regulated genes. Although laboratory studies including the use of animal models have shown that vitamin D has antiprostate cancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be inconclusive and an intensively studied subject. This review will provide up-to-date information regarding the recent outcomes of laboratory and epidemiology studies on the effects of vitamin D on prostate cancer prevention. 1. Introduction The World Health Organization (http://globocan.iarc.fr/factsheets/cancers/prostate.asp) indicates that prostate cancer is the second most frequently diagnosed cancer in men (903,000 new cases) and has about 258,000 deaths of this cancer worldwide in 2008. The highest incident rates are among the countries of Australia/New Zealand Western, Northern Europe, and Northern America, and the lowest age-matched incidence rates are those in South-central Asia. In the USA alone, the American Cancer Society (http://www.cancer.org/Cancer/ProstateCancer/DetailedGuide/prostate-cancer-key-statistics) estimated death and newly diagnosed cases of prostate cancer were 32,050 and 217,730 men, respectively, in year 2010. Moreover, in USA, the total medical expenditure for prostate cancer treatment was estimated as $1.3 billion in year 2000, which represents a 30% increase compared to that in 1994. In year 2004, 2.3 billion was estimated for prostate cancer alone [1]. As being a prevalent cancer disease in men, current total cost for PCa prostate cancer treatments in USA would much exceed $2.3 billion. Until now, etiology of prostate cancer is still largely unknown. However, it has been suggested that there are several potential risk factors that may change incidence rates of this cancer, including diet/nutrition, physical activities, and others [2, 3]. Epidemiologic and laboratory studies in nutrition and diet as modifiable risk factors seem to build strong concepts of cancer chemoprevention, a strategy seeking the reduction of cancer risk by the use of chemical agents
References
[1]
J. Lipscomb, “Estimating the cost of cancer care in the United States: a work very much in progress,” Journal of the National Cancer Institute, vol. 100, no. 9, pp. 607–610, 2008.
[2]
D. G. Bostwick, H. B. Burke, D. Djakiew et al., “Human prostate cancer risk factors,” Cancer, vol. 101, supplement 10, pp. 2371–2490, 2004.
[3]
E. A. Klein, “Chemoprevention of prostate cancer,” Annual Review of Medicine, vol. 57, pp. 49–63, 2006.
[4]
J. F. Lowe and L. A. Frazee, “Update on prostate cancer chemoprevention,” Pharmacotherapy, vol. 26, no. 3, pp. 353–359, 2006.
[5]
S. M. Lippman and J. J. Lee, “Reducing the “risk”of chemoprevention: defining and targeting high risk—2005 AACR cancer research and prevention foundation award lecture,” Cancer Research, vol. 66, no. 6, pp. 2893–2903, 2006.
[6]
S. Shukla and S. Gupta, “Dietary agents in the chemoprevention of prostate cancer,” Nutrition and Cancer, vol. 53, no. 1, pp. 18–32, 2005.
[7]
I. M. Thompson, C. M. Tangen, P. J. Goodman, M. S. Lucia, and E. A. Klein, “Chemoprevention of prostate cancer,” Journal of Urology, vol. 182, no. 2, pp. 499–508, 2009.
[8]
K. A. Kennel, M. T. Drake, and D. L. Hurley, “Vitamin D deficiency in adults: when to test and how to treat,” Mayo Clinic Proceedings, vol. 85, no. 8, pp. 752–757, 2010.
[9]
A. C. Ross, J. E. Manson, S. A. Abrams, et al., “The 2011 report on dietary reference intakes for calcium and vitamin D from the institute of medicine: what clinicians need to know,” The Journal of Clinical Endocrinology & Metabolism, vol. 96, no. 1, pp. 53–58, 2011.
[10]
M. F. Holick, “Vitamin D and sunlight: strategies for cancer prevention and other health benefits,” Clinical Journal of the American Society of Nephrology, vol. 3, no. 5, pp. 1548–1554, 2008.
[11]
C. D. Toner, C. D. Davis, and J. A. Milner, “The vitamin D and cancer conundrum: aiming at a moving target,” Journal of the American Dietetic Association, vol. 110, no. 10, pp. 1492–1500, 2010.
[12]
M. F. Holick, E. Smith, and S. Pincus, “Skin as the site of vitamin D synthesis and target tissue for 1,25-dihydroxyvitamin D3: use of calcitriol (1,25-dihydroxyvitamin D3) for treatment of psoriasis,” Archives of Dermatology, vol. 123, no. 12, pp. 1677–1683, 1987.
[13]
A. W. Norman, “Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D: integral components of the vitamin D endocrine system,” American Journal of Clinical Nutrition, vol. 67, no. 6, pp. 1108–1110, 1998.
[14]
H. H. Glossmann, “Origin of 7-dehydrocholesterol (provitamin D) in the skin,” Journal of Investigative Dermatology, vol. 130, no. 8, pp. 2139–2141, 2010.
[15]
B. A. Ingraham, B. Bragdon, and A. Nohe, “Molecular basis of the potential of vitamin D to prevent cancer,” Current Medical Research and Opinion, vol. 24, no. 1, pp. 139–149, 2008.
[16]
D. Gupta, C. A. Lammersfeld, K. Trukova, and C. G. Lis, “Vitamin D and prostate cancer risk: a review of the epidemiological literature,” Prostate Cancer and Prostatic Diseases, vol. 12, no. 3, pp. 215–226, 2009.
[17]
M. L. McCullough, R. M. Bostick, and T. L. Mayo, “Vitamin D gene pathway polymorphisms and risk of colorectal, breast, and prostate cancer,” Annual Review of Nutrition, vol. 29, pp. 111–132, 2009.
[18]
L. A. Mucci and D. Spiegelman, “Vitamin D and prostate cancer risk—a less sunny outlook?” Journal of the National Cancer Institute, vol. 100, no. 11, pp. 759–761, 2008.
[19]
G. Jones, “Pharmacokinetics of vitamin D toxicity,” American Journal of Clinical Nutrition, vol. 88, no. 2, pp. 582S–586S, 2008.
[20]
S. A. Talwar, J. F. Aloia, S. Pollack, and J. K. Yeh, “Dose response to vitamin D supplementation among postmenopausal African American women,” American Journal of Clinical Nutrition, vol. 86, no. 6, pp. 1657–1662, 2007.
[21]
R. P. Heaney, K. M. Davies, T. C. Chen, M. F. Holick, and M. J. Barger-Lux, “Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol,” American Journal of Clinical Nutrition, vol. 77, no. 1, pp. 204–210, 2003.
[22]
J. F. Aloia, M. Patel, R. DiMaano et al., “Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration,” American Journal of Clinical Nutrition, vol. 87, no. 6, pp. 1952–1958, 2008.
[23]
K. D. Cashman, T. R. Hill, A. J. Lucey et al., “Estimation of the dietary requirement for vitamin D in healthy adults,” American Journal of Clinical Nutrition, vol. 88, no. 6, pp. 1535–1542, 2008.
[24]
H. M. Trang, D. E. Cole, L. A. Rubin, A. Pierratos, S. Siu, and R. Vieth, “Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2,” American Journal of Clinical Nutrition, vol. 68, no. 4, pp. 854–858, 1998.
[25]
L. A. G. Armas, B. W. Hollis, and R. P. Heaney, “Vitamin D2 is much less effective than vitamin D3 in humans,” Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 11, pp. 5387–5391, 2004.
[26]
M. F. Holick, R. M. Biancuzzo, T. C. Chen et al., “Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 3, pp. 677–681, 2008.
[27]
A. C. Looker, “Do body fat and exercise modulate vitamin D status?” Nutrition Reviews, vol. 65, no. 8, pp. S124–S126, 2007.
[28]
L. B. Yanoff, S. J. Parikh, A. Spitalnik et al., “The prevalence of hypovitaminosis D and secondary hyperparathyroidism in obese black Americans,” Clinical Endocrinology, vol. 64, no. 5, pp. 523–529, 2006.
[29]
S. Chennaiah, V. Vijayalakshmi, and C. Suresh, “Effect of the supplementation of dietary rich phytoestrogens in altering the vitamin D levels in diet induced osteoporotic rat model,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 21, no. 1-2, pp. 268–272, 2010.
[30]
H. S. Cross and E. Kallay, “Regulation of the colonic vitamin D system for prevention of tumor progression: an update,” Future Oncology, vol. 5, no. 4, pp. 493–507, 2009.
[31]
A. Hossein-nezhad, K. Mirzaei, Z. Maghbooli, A. Najmafshar, and B. Larijani, “The influence of folic acid supplementation on maternal and fetal bone turnover,” Journal of Bone and Mineral Metabolism, vol. 29, no. 2, pp. 186–192, 2010.
[32]
H. S. Cross, T. Nittke, and M. Peterlik, “Modulation of vitamin D synthesis and catabolism in colorectal mucosa: a new target for cancer preventio,” Anticancer Research, vol. 29, no. 9, pp. 3705–3712, 2009.
[33]
T. C. Chen, “25-hydroxyvitamin D-1 alpha-hydroxylase (CYP27B1) is a new class of tumor suppressor in the prostate,” Anticancer Research, vol. 28, no. 4A, pp. 2015–2017, 2008.
[34]
L. W. Whitlatch, M. V. Young, G. G. Schwartz et al., “25-hydroxyvitamin D-1alpha-hydroxylase activity is diminished in human prostate cancer cells and is enhanced by gene transfer,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 81, no. 2, pp. 135–140, 2002.
[35]
J. Rungby, L. Mortensen, K. Jakobsen, A. Brock, and L. Mosekilde, “Distribution of hydroxylated vitamin D metabolites [25OHD3 and 1,25(OH)2D3] in domestic pigs: evidence that 1,25(OH)2D3] is stored outside the blood circulation?” Comparative Biochemistry and Physiology, vol. 104, no. 3, pp. 483–484, 1993.
[36]
B. R. Konety, G. Somogyi, A. Atan, J. Muindi, M. B. Chancellor, and R. H. Getzenberg, “Evaluation of intraprostatic metabolism of 1,25-dihydroxyvitamin D3 (calcitriol) using a microdialysis technique,” Urology, vol. 59, no. 6, pp. 947–952, 2002.
[37]
Y. R. Lou, S. Qiao, R. Talonpoika, H. Syv？l？, and P. Tuohimaa, “The role of vitamin D3 metabolism in prostate cancer,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 92, no. 4, pp. 317–325, 2004.
[38]
T. C. Chen, L. Wang, L. W. Whitlatch, J. N. Flanagan, and M. F. Holick, “Prostatic 25-hydroxyvitamin D-1alpha-hydroxylase and its implication in prostate cancer,” Journal of Cellular Biochemistry, vol. 88, no. 2, pp. 315–322, 2003.
[39]
J. F. Ma, L. Nonn, M. J. Campbell, M. Hewison, D. Feldman, and D. M. Peehl, “Mechanisms of decreased Vitamin D 1alpha-hydroxylase activity in prostate cancer cells,” Molecular and Cellular Endocrinology, vol. 221, no. 1-2, pp. 67–74, 2004.
[40]
M. Khorchide, D. Lechner, and H. S. Cross, “Epigenetic regulation of vitamin D hydroxylase expression and activity in normal and malignant human prostate cells,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 93, no. 2-5, pp. 167–172, 2005.
[41]
L. Wang, K. S. Persons, D. Jamieson et al., “Prostate 25-hydroxyvitamin D-1alpha-hydroxylase is up-regulated by suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor,” Anticancer Research, vol. 28, no. 4A, pp. 2009–2013, 2008.
[42]
Y. R. Lou, I. Laaksi, H. Syv？l？ et al., “25-hydroxyvitamin D3 is an active hormone in human primary prostatic stromal cells,” The FASEB journal, vol. 18, no. 2, pp. 332–334, 2004.
[43]
R. J. Skowronski, D. M. Peehl, and D. Feldman, “Vitamin D and prostate cancer: 1,25 dihydroxyvitamin D3 receptors and actions in human prostate cancer cell lines,” Endocrinology, vol. 132, no. 5, pp. 1952–1960, 1993.
[44]
G. J. Miller, G. E. Stapleton, T. E. Hedlund, and K. A. Moffatt, “Vitamin D receptor expression, 24-hydroxylase activity, and inhibition of growth by 1alpha,25-dihydroxyvitamin D3 in seven human prostatic carcinoma cell lines,” Clinical Cancer Research, vol. 1, no. 9, pp. 997–1003, 1995.
[45]
W. Luo, A. R. Karpf, K. K. Deeb, et al., “Epigenetic mechanisms of promigratory chemokine CXCL14 regulation in human prostate cancer cells,” Cancer Research, vol. 70, no. 14, pp. 5953–5962, 2010.
[46]
A. Roff and R. T. Wilson, “A novel SNP in a vitamin D response element of the CYP24A1 promoter reduces protein binding, transactivation, and gene expression,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 112, no. 1–3, pp. 47–54, 2008.
[47]
J. R. Muindi, A. Nganga, K. L. Engler, L. J. Coignet, C. S. Johnson, and D. L. Trump, “CYP24 splicing variants are associated with different patterns of constitutive and calcitriol-inducible CYP24 activity in human prostate cancer cell lines,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 103, no. 3–5, pp. 334–337, 2007.
[48]
Y. R. Lou and P. Tuohimaa, “Androgen enhances the antiproliferative activity of vitamin D3 by suppressing 24-hydroxylase expression in LNCaP cells,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 99, no. 1, pp. 44–49, 2006.
[49]
Y. R. Lou, N. Nazarova, R. Talonpoika, et al., “5alpha-dihydrotestosterone inhibits 1alpha,25-dihydroxyvitamin D3-induced expression of CYP24 in human prostate cancer cells,” Prostate, vol. 63, no. 3, pp. 222–230, 2005.
[50]
Y. R. Lou, S. Miettinen, H. Kagechika, H. Gronemeyer, and P. Tuohimaa, “Retinoic acid via RARalpha inhibits the expression of 24-hydroxylase in human prostate stromal cells,” Biochemical and Biophysical Research Communications, vol. 338, no. 4, pp. 1973–1981, 2005.
[51]
H. Farhan, K. W？h？l？, and H. S. Cross, “Genistein inhibits vitamin D hydroxylases CYP24 and CYP27B1 expression in prostate cells,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 84, no. 4, pp. 423–429, 2003.
[52]
S. Swami, A. V. Krishnan, D. M. Peehl, and D. Feldman, “Genistein potentiates the growth inhibitory effects of 1,25-dihydroxyvitamin D3 in DU145 human prostate cancer cells: role of the direct inhibition of CYP24 enzyme activity,” Molecular and Cellular Endocrinology, vol. 241, no. 1-2, pp. 49–61, 2005.
[53]
J. R. Muindi, Y. u. WD, Y. Ma, et al., “CYP24A1 inhibition enhances the antitumor activity of calcitriol,” Endocrinology, vol. 151, no. 9, pp. 4301–4312, 2010.
[54]
A. V. Krishnan, D. L. Trump, C. S. Johnson, and D. Feldman, “The role of vitamin D in cancer prevention and treatment,” Endocrinology and Metabolism Clinics of North America, vol. 39, no. 2, pp. 401–418, 2010.
[55]
J. W. Pike and M. B. Meyer, “The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D3,” Endocrinology and Metabolism Clinics of North America, vol. 39, no. 2, pp. 255–269, 2010.
[56]
M. T. Mizwicki and A. W. Norman, “The vitamin D sterol-vitamin D receptor ensemble model offers unique insights into both genomic and rapid-response signaling,” Science Signaling, vol. 2, no. 75, p. re4, 2009.
[57]
Z. Zhang, P. Kovalenko, M. Cui, M. Desmet, S. K. Clinton, and J. C. Fleet, “Constitutive activation of the mitogen-activated protein kinase pathway impairs vitamin D signaling in human prostate epithelial cells,” Journal of Cellular Physiology, vol. 224, no. 2, pp. 433–442, 2010.
[58]
N. J. Koszewski, J. Herberth, and H. H. Malluche, “Retinoic acid receptor gamma 2 interactions with vitamin D response elements,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 120, no. 4-5, pp. 200–207, 2010.
[59]
S. Murthy, I. U. Agoulnik, and N. L. Weigel, “Androgen receptor signaling and vitamin D receptor action in prostate cancer cells,” Prostate, vol. 64, no. 4, pp. 362–372, 2005.
[60]
S. Mordan-McCombs, T. Brown, W. L. Wang, A. C. Gaupel, J. Welsh, and M. Tenniswood, “Tumor progression in the LPB-Tag transgenic model of prostate cancer is altered by vitamin D receptor and serum testosterone status,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 121, no. 1-2, pp. 368–371, 2010.
[61]
L. P. Zanello and A. W. Norman, “Rapid modulation of osteoblast ion channel responses by 1alpha,25(OH)2-vitamin D3 requires the presence of a functional vitamin D nuclear receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 6, pp. 1589–1594, 2004.
[62]
C. Crescioli, M. Maggi, G. B. Vannelli et al., “Effect of a vitamin D3 analogue on keratinocyte growth factor-induced cell proliferation in benign prostate hyperplasia,” Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 7, pp. 2576–2583, 2000.
[63]
T. E. Hedlund, K. A. Moffatt, and G. J. Miller, “Stable expression of the nuclear vitamin D receptor in the human prostatic carcinoma cell line JCA-1: evidence that the antiproliferative effects of 1 alpha, 25-dihydroxyvitamin D3 are mediated exclusively through the genomic signaling pathway,” Endocrinology, vol. 137, no. 5, pp. 1554–1561, 1996.
[64]
H. A. Pedrozo, Z. Schwartz, S. Rimes et al., “Physiological importance of the 1,25(OH)2D3membrane receptor and evidence for a membrane receptor specific for 24,25(OH)2D3,” Journal of Bone and Mineral Research, vol. 14, no. 6, pp. 856–867, 1999.
[65]
I. Nemere, M. C. Farach-Carson, B. Rohe et al., “Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS) and phosphate uptake in intestinal cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 19, pp. 7392–7397, 2004.
[66]
S. Karlsson, J. Olausson, D. Lundh et al., “Vitamin D and prostate cancer: the role of membrane initiated signaling pathways in prostate cancer progression,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 121, no. 1-2, pp. 413–416, 2010.
[67]
A. V. Krishnan and D. Feldman, “Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment,” Endocrine-Related Cancer, vol. 17, no. 1, pp. R19–R38, 2010.
[68]
E. Gocek and G. P. Studzinski, “Vitamin D and differentiation in cancer signaling differentiation,” Critical Reviews in Clinical Laboratory Sciences, vol. 46, no. 4, pp. 190–209, 2009.
[69]
J. N. Rohan and N. L. Weigel, “1α,25-dihydroxyvitamin D3 reduces c-Myc expression, inhibiting proliferation and causing G1 accumulation in C4-2 prostate cancer cells,” Endocrinology, vol. 150, no. 5, pp. 2046–2054, 2009.
[70]
S. Toropainen, S. V？is？nen, S. Heikkinen, and C. Carlberg, “The down-regulation of the human MYC gene by the nuclear hormone 1alpha,25-dihydroxyvitamin D3 is associated with cycling of corepressors and histone deacetylases,” Journal of Molecular Biology, vol. 400, no. 3, pp. 284–294, 2010.
[71]
N. Ikeda, H. Uemura, H. Ishiguro et al., “Combination treatment with 1alpha,25-dihydroxyvitamin D3 and 9-cis-retinoic acid directly inhibits human telomerase reverse transcriptase transcription in prostate cancer cells,” Molecular Cancer Therapeutics, vol. 2, no. 8, pp. 739–746, 2003.
[72]
S. E. Blutt, T. J. Mcdonnell, T. C. Polek, and N. L. Weigel, “Calcitriol-induced apoptosis in LNCaP cells is blocked by overexpression of Bcl-2,” Endocrinology, vol. 141, no. 1, pp. 10–17, 2000.
[73]
V. Sung and D. Feldman, “1,25-Dihydroxyvitamin D3 decreases human prostate cancer cell adhesion and migration,” Molecular and Cellular Endocrinology, vol. 164, no. 1-2, pp. 133–143, 2000.
[74]
E. S. Yang and K. L. Burnstein, “Vitamin D inhibits G1 to S progression in LNCaP prostate cancer cells through p27Kip1 stabilization and Cdk2 mislocalization to the cytoplasm,” Journal of Biological Chemistry, vol. 278, no. 47, pp. 46862–46868, 2003.
[75]
S. S. Jensen, M. W. Madsen, J. Lukas, L. Binderup, and J. Bartek, “Inhibitory effects of 1 ,25-dihydroxyvitamin D3 on the G1-S phase-controlling machinery,” Molecular Endocrinology, vol. 15, no. 8, pp. 1370–1380, 2001.
[76]
M. Liu, M. H. Lee, M. Cohen, M. Bommakanti, and L. P. Freedman, “Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937,” Genes and Development, vol. 10, no. 2, pp. 142–153, 1996.
[77]
S. E. Blutt, E. A. Allegretto, J. W. Pike, and N. L. Weigel, “1,25-dihydroxyvitamin D3and 9-cis-acid act synergistically to inhibit the growth of LNCaP prostate cells and cause accumulation of cells in G1,” Endocrinology, vol. 138, no. 4, pp. 1491–1497, 1997.
[78]
M. J. Campbell, E. Elstner, S. Holden, M. Uskokovic, and H. P. Koeffler, “Inhibition of proliferation of prostate cancer cells by a 19-nor-hexafluoride vitamin D3 analogue involves the induction of p21waf1, p27kip1 and E-cadherin,” Journal of Molecular Endocrinology, vol. 19, no. 1, pp. 15–27, 1997.
[79]
O. Flores and K. L. Burnstein, “GADD45gamma: a new vitamin D-regulated gene that is antiproliferative in prostate cancer cells,” Endocrinology, vol. 151, no. 10, pp. 4654–4664, 2010.
[80]
B. Y. Bao, S. D. Yeh, and Y. F. Lee, “1alpha,25-dihydroxyvitamin D3 inhibits prostate cancer cell invasion via modulation of selective proteases,” Carcinogenesis, vol. 27, no. 1, pp. 32–42, 2006.
[81]
Z. Culig, H. Steiner, G. Bartsch, and A. Hobisch, “Interleukin-6 regulation of prostate cancer cell growth,” Journal of Cellular Biochemistry, vol. 95, no. 3, pp. 497–505, 2005.
[82]
B. Wegiel, A. Bjartell, Z. Culig, and J. L. Persson, “Interleukin-6 activates PI3K/Akt pathway and regulates cyclin A1 to promote prostate cancer cell survival,” International Journal of Cancer, vol. 122, no. 7, pp. 1521–1529, 2008.
[83]
S. Araki, Y. Omori, D. Lyn et al., “Interleukin-8 is a molecular determinant of androgen independence and progression in prostate cancer,” Cancer Research, vol. 67, no. 14, pp. 6854–6862, 2007.
[84]
S. Vasto, G. Carruba, G. Candore, E. Italiano, D. Di Bona, and C. Caruso, “Inflammation and prostate cancer,” Future Oncology, vol. 4, no. 5, pp. 637–645, 2008.
[85]
D. J. Mantell, P. E. Owens, N. J. Bundred, E. B. Mawer, and A. E. Canfield, “1 ,25-dihydroxyvitamin D3 inhibits angiogenesis in vitro and in vivo,” Circulation Research, vol. 87, no. 3, pp. 214–220, 2000.
[86]
L. Nonn, L. Peng, D. Feldman, and D. M. Peehl, “Inhibition of p38 by vitamin D reduces interleukin-6 production in normal prostate cells via mitogen-activated protein kinase phosphatase 5: implications for prostate cancer prevention by vitamin D,” Cancer Research, vol. 66, no. 8, pp. 4516–4524, 2006.
[87]
B. Y. Bao, J. Yao, and Y. F. Lee, “1alpha, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis,” Carcinogenesis, vol. 27, no. 9, pp. 1883–1893, 2006.
[88]
Y. Xu, F. Fang, D. K. Clair et al., “Suppression of RelB-mediated manganese superoxide dismutase expression reveals a primary mechanism for radiosensitization effect of 1alpha,25-dihydroxyvitamin D3 in prostate cancer cells,” Molecular Cancer Therapeutics, vol. 6, no. 7, pp. 2048–2056, 2007.
[89]
M. Ben-Shoshan, S. Amir, D. T. Dang, L. H. Dang, Y. Weisman, and N. J. Mabjeesh, “1α,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells,” Molecular Cancer Therapeutics, vol. 6, no. 4, pp. 1433–1439, 2007.
[90]
I. Chung, G. Han, M. Seshadri et al., “Role of vitamin D receptor in the antiproliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo,” Cancer Research, vol. 69, no. 3, pp. 967–975, 2009.
[91]
J. Moreno, A. V. Krishnan, S. Swami, L. Nonn, D. M. Peehl, and D. Feldman, “Regulation of prostaglandin metabolism by calcitriol attenuates growth stimulation in prostate cancer cell,” Cancer Research, vol. 65, no. 17, pp. 7917–7925, 2005.
[92]
A. V. Krishnan, J. Moreno, L. Nonn et al., “Novel pathways that contribute to the anti-proliferative and chemopreventive activities of calcitriol in prostate cancer,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 103, no. 3–5, pp. 694–702, 2007.
[93]
A. V. Krishnan, S. Srinivas, D. Feldman, et al., “Inhibition of prostaglandin synthesis and actions contributes to the beneficial effects of calcitriol in prostate cancer,” Dermato-Endocrinology, vol. 1, no. 1, pp. 7–11, 2009.
[94]
H. van der Rhee, J. W. Coebergh, and E. D. Vries, “Sunlight, vitamin D and the prevention of cancer: a systematic review of epidemiological studies,” European Journal of Cancer Prevention, vol. 18, pp. 458–475, 2009.
[95]
E. M. John, J. Koo, and G. G. Schwartz, “Sun exposure and prostate cancer risk: evidence for a protective effect of early-life exposure,” Cancer Epidemiology Biomarkers and Prevention, vol. 16, no. 6, pp. 1283–1286, 2007.
[96]
C. L. Hanchette and G. G. Schwartz, “Geographic patterns of prostate cancer mortality. evidence for a protective effect of ultraviolet radiation,” Cancer, vol. 70, no. 12, pp. 2861–2869, 1992.
[97]
G. G. Schwartz and C. L. Hanchette, “UV, latitude, and spatial trends in prostate cancer mortality: all sunlight is not the same (United States),” Cancer Causes and Control, vol. 17, no. 8, pp. 1091–1101, 2006.
[98]
W. B. Grant, “An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation,” Cancer, vol. 94, no. 6, pp. 1867–1875, 2002.
[99]
C. J. Luscombe, A. A. Fryer, M. E. French et al., “Exposure to ultraviolet radiation: association with susceptibility and age at presentation with prostate cancer,” The Lancet, vol. 358, no. 9282, pp. 641–642, 2001.
[100]
E. M. John, D. M. Dreon, J. Koo, et al., “Residential sunlight exposure is associated with a decreased risk of prostate cancer,” Journal of Steroid Biochemistry & Molecular Biology, vol. 89-90, no. 1–5, pp. 549–552, 2004.
[101]
D. Bodiwala, C. J. Luscombe, M. E. French, et al., “Susceptibility to prostate cancer: studies on interactions between UVR exposure and skin type,” Carcinogenesis, vol. 24, no. 4, pp. 711–717, 2003.
[102]
Z. Lagunova, A. C. Porojnicu, A. Dahlback, J. P. Berg, T. M. Beer, and J. Moan, “Prostate cancer survival is dependent on season of diagnosis,” Prostate, vol. 67, no. 12, pp. 1362–1370, 2007.
[103]
T. E. Robsahm, S. Tretli, A. Dahlback, and J. Moan, “Vitamin D3 from sunlight may improve the prognosis of breast-, colon- and prostate cancer (Norway),” Cancer Causes and Control, vol. 15, no. 2, pp. 149–158, 2004.
[104]
J. L. Colli and A. Colli, “International comparisons of prostate cancer mortality rates with dietary practices and sunlight levels,” Urologic Oncology, vol. 24, no. 3, pp. 184–194, 2006.
[105]
Y. Ben-Shlomo, S. Evans, F. Ibrahim et al., “The risk of prostate cancer amongst black men in the United Kingdom: the process cohort study,” European Urology, vol. 53, no. 1, pp. 99–105, 2008.
[106]
D. Bodiwala, C. J. Luscombe, M. E. French et al., “Polymorphisms in the vitamin D receptor gene, ultraviolet radiation, and susceptibility to prostate cancer,” Environmental and Molecular Mutagenesis, vol. 43, no. 2, pp. 121–127, 2004.
[107]
S. Moon, S. Holley, D. Bodiwala, et al., “Associations between G/A1229, A/G3944, T/C30875, C/T48200 and C/T65013 genotypes and haplotypes in the vitamin D receptor gene, ultraviolet radiation and susceptibility to prostate cancer,” Annals of Human Genetics, vol. 70, pp. 226–236, 2006.
[108]
C. J. Luscombe, M. E. French, S. Liu et al., “Outcome in prostate cancer associations with skin type and polymorphism in pigmentation-related genes,” Carcinogenesis, vol. 22, no. 9, pp. 1343–1347, 2001.
[109]
N. Rukin, M. Blagojevic, C. J. Luscombe, et al., “Associations between timing of exposure to ultraviolet radiation, T-stage and survival in prostate cancer,” Cancer Detection and Prevention Journal, vol. 31, no. 6, pp. 443–449, 2007.
[110]
J. L. Colli and W. B. Grant, “Solar ultraviolet B radiation compared with prostate cancer incidence and mortality rates in United States,” Urology, vol. 71, no. 3, pp. 531–535, 2008.
[111]
E. de Vries, I. Soerjomataram, S. Houterman, et al., “Decreased risk of prostate cancer after skin cancer diagnosis: a protective role of ultraviolet radiation?” American Journal of Epidemiology, vol. 165, no. 8, pp. 966–972, 2007.
[112]
N. J. Rukin, M. P. Zeegers, S. Ramachandran et al., “A comparison of sunlight exposure in men with prostate cancer and basal cell carcinoma,” British Journal of Cancer, vol. 96, no. 3, pp. 523–528, 2007.
[113]
P. Tuohimaa, E. Pukkala, G. Scélo et al., “Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: vitamin D as a possible explanation,” European Journal of Cancer, vol. 43, no. 11, pp. 1701–1712, 2007.
[114]
F. Levi, L. Randimbison, V. C. Te, M. M. Conconi, and C. La Vecchia, “Risk of prostate, breast and colorectal cancer after skin cancer diagnosis,” International Journal of Cancer, vol. 123, no. 12, pp. 2899–2901, 2008.
[115]
R. Gilbert, C. Metcalfe, S. E. Oliver et al., “Life course sun exposure and risk of prostate cancer: population-based nested case-control study and meta-analysis,” International Journal of Cancer, vol. 125, no. 6, pp. 1414–1423, 2009.
[116]
W. B. Grant, “Geographic variation of prostate cancer mortality rates in the United States: implications for prostate cancer risk related to vitamin D,” International Journal of Cancer, vol. 111, no. 3, pp. 470–471, 2004.
[117]
P. Waltz and G. Chodick, “International comparisons of prostate cancer mortality rates with dietary practices and sunlight levels,” Urologic Oncology, vol. 25, no. 1, p. 85, 2007.
[118]
P. Waltz and G. Chodick, “Assessment of ecological regression in the study of colon, breast, ovary, non-Hodgkin's lymphoma, or prostate cancer and residential UV,” European Journal of Cancer Prevention, vol. 17, no. 3, pp. 279–286, 2008.
[119]
E. H. Corder, H. A. Guess, B. S. Hulka et al., “Vitamin D and prostate cancer: a prediagnostic study with stored sera,” Cancer Epidemiology Biomarkers and Prevention, vol. 2, no. 5, pp. 467–472, 1993.
[120]
M. H. Ahonen, L. Tenkanen, L. Teppo, M. Hakama, and P. Tuohimaa, “Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland),” Cancer Causes and Control, vol. 11, no. 9, pp. 847–852, 2000.
[121]
H. Li, M. J. Stampfer, J. B. Hollis et al., “A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer,” PLoS Medicine, vol. 4, no. 3, article e103, 2007.
[122]
S. Tretli, E. Hernes, J. P. Berg, U. E. Hestvik, and T. E. Robsahm, “Association between serum 25(OH)D and death from prostate cancer,” British Journal of Cancer, vol. 100, no. 3, pp. 450–454, 2009.
[123]
M. M. Braun, K. J. Helzlsouer, B. W. Hollis, and G. W. Comstock, “Prostate cancer and prediagnostic levels of serum vitamin D metabolites (Maryland, United States),” Cancer Causes and Control, vol. 6, no. 3, pp. 235–239, 1995.
[124]
P. H. Gann, J. Ma, C. H. Hennekens, et al., “Circulating vitamin D metabolites in relation to subsequent development of prostate cancer,” Cancer Epidemiology, Biomarkers & Prevention, vol. 5, no. 2, pp. 121–126, 1996.
[125]
A. M. Nomura, G. N. Stemmermann, J. Lee et al., “Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States),” Cancer Causes and Control, vol. 9, no. 4, pp. 425–432, 1998.
[126]
E. A. Platz, M. F. Leitzmann, B. W. Hollis, W. C. Willett, and E. Giovannucci, “Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer,” Cancer Causes and Control, vol. 15, no. 3, pp. 255–265, 2004.
[127]
S. Gandini, M. Boniol, J. Haukka, et al., “Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma,” International Journal of Cancer, vol. 128, no. 6, pp. 1414–1424, 2011.
[128]
C. M. Barnett, C. M. Nielson, J. Shannon et al., “Serum 25-OH vitamin D levels and risk of developing prostate cancer in older men,” Cancer Causes and Control, vol. 21, no. 8, pp. 1297–1303, 2010.
[129]
R. C. Travis, F. L. Crowe, N. E. Allen 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),” American Journal of Epidemiology, vol. 169, no. 10, pp. 1223–1232, 2009.
[130]
J. Ahn, U. Peters, D. Albanes, et al., “Serum vitamin D concentration and prostate cancer risk: a nested case-control study,” Journal of the National Cancer Institute, vol. 100, no. 11, pp. 796–804, 2008.
[131]
P. Tuohimaa, L. Tenkanen, M. Ahonen, 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,” International Journal of Cancer, vol. 108, no. 1, pp. 104–108, 2004.
[132]
B. Mikhak, D. J. Hunter, D. Spiegelman, E. A. Platz, B. W. Hollis, and E. Giovannucci, “Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk,” Prostate, vol. 67, no. 9, pp. 911–923, 2007.
[133]
J. Ma, M. J. Stampfer, P. H. Gann et al., “Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians,” Cancer Epidemiology Biomarkers and Prevention, vol. 7, no. 5, pp. 385–390, 1998.
[134]
S. Y. Park, S. P. Murphy, L. R. Wilkens, D. O. Stram, B. E. Henderson, and L. N. Kolonel, “Calcium, vitamin D, and dairy product intake and prostate cancer risk: the multiethnic cohort study,” American Journal of Epidemiology, vol. 166, no. 11, pp. 1259–1269, 2007.
[135]
A. R. Kristal, K. B. Arnold, M. L. Neuhouser et al., “Diet, supplement use, and prostate cancer risk: results from the prostate cancer prevention trial,” American Journal of Epidemiology, vol. 172, no. 5, pp. 566–577, 2010.
[136]
M. Huncharek, J. Muscat, and B. Kupelnick, “Dairy products, dietary calcium and vitamin D intake as risk factors for prostate cancer: a meta-analysis of 26,769 cases from 45 observational studies,” Nutrition and Cancer, vol. 60, no. 4, pp. 421–441, 2008.
[137]
A. G. Uitterlinden, Y. Fang, J. B. Van Meurs, H. A. P. Pols, and J. P. T. M. Van Leeuwen, “Genetics and biology of vitamin D receptor polymorphisms,” Gene, vol. 338, no. 2, pp. 143–156, 2004.
[138]
L. Gennari, V. De Paola, D. Merlotti, G. Martini, and R. Nuti, “Steroid hormone receptor gene polymorphisms and osteoporosis: a pharmacogenomic review,” Expert Opinion on Pharmacotherapy, vol. 8, no. 5, pp. 537–553, 2007.
[139]
G. K. Whitfield, L. S. Remus, P. W. Jurutka et al., “Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene,” Molecular and Cellular Endocrinology, vol. 177, no. 1-2, pp. 145–159, 2001.
[140]
S. M. Orton, A. P. Morris, B. M. Herrera et al., “Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis,” American Journal of Clinical Nutrition, vol. 88, no. 2, pp. 441–447, 2008.
[141]
H. Arai, K. I. Miyamoto, M. Yoshida et al., “The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene,” Journal of Bone and Mineral Research, vol. 16, no. 7, pp. 1256–1264, 2001.
[142]
L. K. Durrin, R. W. Haile, S. A. Ingles, and G. A. Coetzee, “Vitamin D receptor 3'-untranslated region polymorphisms: lack of effect on mRNA stability,” Biochimica et Biophysica Acta, vol. 1453, no. 3, pp. 311–320, 1999.
[143]
T. Carling, J. Rastad, G. Akerstr？m, and G. Westin, “Vitamin D receptor (VDR) and parathyroid hormone messenger ribonucleic acid levels correspond to polymorphic VDR alleles in human parathyroid tumors,” Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 7, pp. 2255–2259, 1998.
[144]
W. Verbeek, A. F. Gombart, M. Shiohara, et al., “Vitamin D receptor: no evidence for allele-specific mRNA stability in cells which are heterozygous for the Taq I restriction enzyme polymorphism,” Biochemical and Biophysical Research Communications, vol. 238, no. 1, pp. 77–80, 1997.
[145]
N. A. Morrison, J. C. Qi, A. Tokita et al., “Prediction of bone density from vitamin D receptor alleles,” Nature, vol. 387, no. 6628, p. 106, 1994.
[146]
J. A. Taylor, A. Hirvonen, M. Watson, G. Pittman, J. L. Mohler, and D. A. Bell, “Association of prostate cancer with vitamin D receptor gene polymorphism,” Cancer Research, vol. 56, no. 18, pp. 4108–4110, 1996.
[147]
S. A. Ingles, R. K. Ross, M. C. Yu et al., “Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor,” Journal of the National Cancer Institute, vol. 89, no. 2, pp. 166–170, 1997.
[148]
T. Habuchi, T. Suzuki, R. Sasaki et al., “Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population,” Cancer Research, vol. 60, no. 2, pp. 305–308, 2000.
[149]
K. Suzuki, H. Matsui, N. Ohtake et al., “Vitamin D receptor gene polymorphism in familial prostate cancer in a Japanese population,” International Journal of Urology, vol. 10, no. 5, pp. 261–266, 2003.
[150]
C. Ntais, A. Polycarpou, and J. P. Ioannidis, “Vitamin D receptor gene polymorphisms and risk of prostate cancer: a meta-analysis,” Cancer Epidemiology Biomarkers and Prevention, vol. 12, no. 12, pp. 1395–1402, 2003.
[151]
I. Oakley-Girvan, D. Feldman, T. R. Eccleshall et al., “Risk of early-onset prostate cancer in relation to germ line polymorphisms of the vitamin D receptor,” Cancer Epidemiology Biomarkers and Prevention, vol. 13, no. 8, pp. 1325–1330, 2004.
[152]
S. Maistro, I. Snitcovsky, A. S. Sarkis, I. A. da Silva, and M. M. Brentani, “Vitamin D receptor polymorphisms and prostate cancer risk in Brazilian men,” International Journal of Biological Markers, vol. 19, no. 3, pp. 245–249, 2004.
[153]
M. B. Cheteri, J. L. Stanford, D. M. Friedrichsen et al., “Vitamin D receptor gene polymorphisms and prostate cancer risk,” Prostate, vol. 59, no. 4, pp. 409–418, 2004.
[154]
S. P. Huang, Y. H. Chou, W. S. Wayne Chang, et al., “Association between vitamin D receptor polymorphisms and prostate cancer risk in a Taiwanese population,” Cancer Letters, vol. 207, no. 1, pp. 69–77, 2004.
[155]
H. Williams, I. J. Powell, S. J. Land, et al., “Vitamin D receptor gene polymorphisms and disease free survival after radical prostatectomy,” Prostate, vol. 61, no. 3, pp. 267–275, 2004.
[156]
E. M. John, G. G. Schwartz, J. Koo, et al., “Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer,” Cancer Research, vol. 65, no. 12, pp. 5470–5479, 2005.
[157]
D. K. Mishra, H. K. Bid, D. S. Srivastava, A. Mandhani, and R. D. Mittal, “Association of vitamin D receptor gene polymorphism and risk of prostate cancer in India,” Urologia Internationalis, vol. 74, no. 4, pp. 315–318, 2005.
[158]
V. M. Hayes, G. Severi, E. J. Padilla et al., “Genetic variants in the vitamin D receptor gene and prostate cancer risk,” Cancer Epidemiology Biomarkers and Prevention, vol. 14, no. 4, pp. 997–999, 2005.
[159]
L. C. Kidd, D. N. Paltoo, S. Wang et al., “Sequence variation within the 5' regulatory regions of the vitamin D binding protein and receptor genes and prostate cancer risk,” Prostate, vol. 64, no. 3, pp. 272–282, 2005.
[160]
S. I. Berndt, J. L. Dodson, W. Y. Huang, and K. K. Nicodemus, “Systematic review of vitamin D receptor gene polymorphisms and prostate cancer risk,” Journal of Urology, vol. 175, no. 5, pp. 1613–1623, 2006.
[161]
C. N. Holick, J. L. Stanford, E. M. Kwon, et al., “Comprehensive association analysis of the vitamin D pathway genes, VDR, CYP27B1, and CYP24A1, in prostate cancer,” Cancer Epidemiology, Biomarkers & Prevention, vol. 16, no. 10, pp. 1990–1999, 2007.
[162]
H. Li, M. J. Stampfer, J. B. Hollis et al., “A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer,” PLoS Medicine, vol. 4, no. 3, article e103, 2007.
[163]
N. J. Rukin, C. Luscombe, S. Moon, et al., “Prostate cancer susceptibility is mediated by interactions between exposure to ultraviolet radiation and polymorphisms in the 5' haplotype block of the vitamin D receptor gene,” Cancer Letters, vol. 247, no. 2, pp. 328–335, 2007.
[164]
I. H. Onen, A. Ekmekci, M. Eroglu, et al., “Association of genetic polymorphisms in vitamin D receptor gene and susceptibility to sporadic prostate cance,” Experimental Biology and Medicine, vol. 233, no. 12, pp. 1608–1614, 2008.
[165]
K. C. Torkko, A. van Bokhoven, P. Mai et al., “VDR and SRD5A2 polymorphisms combine to increase risk for prostate cancer in both non-hispanic white and hispanic white men,” Clinical Cancer Research, vol. 14, no. 10, pp. 3223–3229, 2008.
[166]
J. Ahn, D. Albanes, S. I. Berndt et al., “Vitamin D-related genes, serum vitamin D concentrations and prostate cancer risk,” Carcinogenesis, vol. 30, no. 5, pp. 769–776, 2009.
[167]
L. Chen, G. D. Smith, D. M. Evans, et al., “Genetic variants in the vitamin d receptor are associated with advanced prostate cancer at diagnosis: findings from the prostate testing for cancer and treatment study and a systematic review,” Cancer Epidemiology, Biomarkers & Prevention, vol. 18, no. 11, pp. 2874–2881, 2009.
[168]
S. Raimondi, H. Johansson, P. Maisonneuve, and S. Gandini, “Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk,” Carcinogenesis, vol. 30, no. 7, pp. 1170–1180, 2009.
[169]
M. Yin, S. Wei, and Q. Wei, “Vitamin D receptor genetic polymorphisms and prostate cancer risk: a meta-analysis of 36 published studies,” International Journal of Clinical and Experimental Medicine, vol. 2, no. 2, pp. 159–175, 2009.
[170]
S. K. Holt, E. M. Kwon, U. Peters, E. A. Ostrander, and J. L. Stanford, “Vitamin D pathway gene variants and prostate cancer risk,” Cancer Epidemiology Biomarkers and Prevention, vol. 18, no. 6, pp. 1929–1933, 2009.
[171]
Y. Bai, Y. Yu, B. Yu, et al., “Association of vitamin D receptor polymorphisms with the risk of prostate cancer in the Han population of Southern China,” BMC Medical Genetics, vol. 10, article 125, 2009.
[172]
M. Risio, T. Venesio, E. Kolomoets, et al., “Genetic polymorphisms of CYP17A1, vitamin D receptor and androgen receptor in Italian heredo-familial and sporadic prostate cancers,” Cancer Epidemiology. In press.
