Top

Reviews in Endocrine and Metabolic Disorders

Published in:

01-06-2017

The roles of UVB and vitamin D in reducing risk of cancer incidence and mortality: A review of the epidemiology, clinical trials, and mechanisms

Authors: Meis Moukayed, William B. Grant

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 2/2017

Abstract

Global cancer incidence and mortality rates are high and increasing. Thus, it is imperative to find novel solutions to preventing cancer incidence and treating it at an affordable yet efficacious manner. The solar UVB-vitamin D-cancer hypothesis was first proposed in 1980 based on a geographical ecological study. Since then, numerous ecological and observational studies as well as studies of mechanisms have provided support for the hypothesis. However, observational studies have not provided consistent support, in part due to using a single blood draw from any season to use for serum 25-hydroxyvitamin D [25(OH)D] concentration in prospective studies with long follow-up times. Case-controls studies, in which blood is drawn near time of diagnosis, and prospective studies in which blood is drawn in the sunnier half of the year, are more likely to find significant inverse relations between 25(OH)D and cancer incidence. Three vitamin D plus calcium clinical trials have found significant reduction in all-cancer incidence. This paper reviews the evidence for vitamin D in reducing incidence of and increasing survival from breast, colorectal, lung, ovarian, pancreatic, and prostate cancer. The epidemiological evidence provides strong support for all of these types of cancer except for non-aggressive prostate cancer. Studies of the cellular mechanisms of vitamin D action in different cancer cell types, strongly indicate that vitamin D can exert protective and anti-tumorigenic activities that would retard cellular transformation, hyperplasia and cancer progression. Based on the scientific evidence reviewed in this paper, individuals and health providers can consider increasing 25(OH)D concentrations through sensible sun exposure and/or vitamin D supplementation to reduce risk of and, in conjunction with standard care, treat cancer. Public health acceptance of vitamin D for cancer prevention and treatment requires stronger support from vitamin D clinical trials.

GLOBOCAN. 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. International Agency for Research on Cancer: World Health Organization; 2016.

Global, Regional, and National life Expectancy. All-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1459–544. doi:10.1016/S0140-6736(16)31012-1.CrossRef

Grant WB. Roles of solar UVB and vitamin D in reducing cancer risk and increasing survival. Anticancer Res. 2016;36(3):1357–70.PubMed

Ma Y, Johnson CS, Trump DL. Mechanistic insights of vitamin D anticancer effects. Vitam Horm. 2016;100:395–431. doi:10.1016/bs.vh.2015.11.003.PubMedCrossRef

Dilworth FJ, Scott I, Green A, Strugnell S, Guo YD, Roberts EA, et al. Different mechanisms of hydroxylation site selection by liver and kidney cytochrome P450 species (CYP27 and CYP24) involved in vitamin D metabolism. J Biol Chem. 1995;270(28):16766–74.PubMedCrossRef

Guo YD, Strugnell S, Back DW, Jones G. Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs at different side-chain positions. Proc Natl Acad Sci U S A. 1993;90(18):8668–72.PubMedPubMedCentralCrossRef

McCollum EV. The paths to the discovery of vitamins A and D. J Nutr. 1967;91(2) Suppl 1:11–6.

Holick MF, Richtand NM, McNeill SC, Holick SA, Frommer JE, Henley JW, et al. Isolation and identification of previtamin D3 from the skin of rats exposed to ultraviolet irradiation. Biochemistry. 1979;18(6):1003–8.PubMedCrossRef

Holick MF, MacLaughlin JA, Clark MB, Holick SA, Potts Jr JT, Anderson RR, et al. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science. 1980;210(4466):203–5.PubMedCrossRef

10.

Deluca HF. History of the discovery of vitamin D and its active metabolites. Bonekey Rep. 2014;3:479. doi:10.1038/bonekey.2013.213.PubMedPubMedCentral

11.

Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer. 2007;7(9):684–700. doi:10.1038/nrc2196.PubMedCrossRef

12.

Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29(6):726–76.PubMedPubMedCentralCrossRef

13.

Moukayed M, Grant WB. Molecular link between vitamin D and cancer prevention. Nutrition. 2013;5(10):3993–4021. doi:10.3390/nu5103993.

14.

Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res Off J Am Soc Bone Miner Res. 1998;13(3):325–49.CrossRef

15.

Christakos S, Dhawan P, Liu Y, Peng X, Porta A. New insights into the mechanisms of vitamin D action. J Cell Biochem. 2003;88(4):695–705.PubMedCrossRef

16.

Zanatta L, Bouraima-Lelong H, Delalande C, Silva FR, Carreau S. Regulation of aromatase expression by 1alpha,25(OH)2 vitamin D3 in rat testicular cells. Reprod Fertil Dev. 2011;23(5):725–35.PubMedCrossRef

17.

Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, et al. The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev. 2012;33(3):456–92.PubMedPubMedCentralCrossRef

18.

Baran DT, Sorensen AM. Rapid actions of 1 alpha-25-dihydroxyvitamin D3 physiologic role. Proc Soc Exp Biol Med. 1994;207(2):175–9.PubMedCrossRef

19.

Shi H, Norman AW, Okamura WH, Sen A, Zemel MB. 1alpha,25-dihydroxyvitamin D3 modulates human adipocyte metabolism via nongenomic action. FASEB journal : Official Publication of the Federation of American Societies for Experimental Biology. 2001;15(14):2751–3.

20.

Tomlinson IP, Lambros MB, Roylance RR. Loss of heterozygosity analysis: practically and conceptually flawed? Genes Chromosom Cancer. 2002;34(4):349–53.PubMedCrossRef

21.

Testa JR, Hino O. Tumor suppressor genes and the two-hit model of recessive oncogenesis: celebrating Alfred Knudson's 80th birthday. Genes Chromosom Cancer. 2003;38(4):286–7.PubMedCrossRef

22.

Diaz-Cano SJ. Pathological bases for a robust application of cancer molecular classification. Int J Mol Sci. 2015;16(4):8655–75. doi:10.3390/ijms16048655.PubMedPubMedCentralCrossRef

23.

Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer. 1997;33(5):787–91.PubMedCrossRef

24.

Takeishi S, Nakayama KI. To wake up cancer stem cells, or to let them sleep, that is the question. Cancer Sci. 2016;107(7):875–81.PubMedPubMedCentralCrossRef

25.

Lopez-Bertoni H, Li Y, Laterra J. Cancer stem cells: dynamic entities in an ever-evolving paradigm. Biol Med (Aligarh). 2015;7(Suppl 2):pii: 001.

26.

Maruthanila VL, Elancheran R, Kunnumakkara AB, Kabilan S, Kotoky J. Recent development of targeted approaches for the treatment of breast cancer. Breast Cancer. 2016. doi:10.1007/s12282-016-0732-1.

27.

Rani V, Deep G, Singh RK, Palle K, Yadav UC. Oxidative stress and metabolic disorders: pathogenesis and therapeutic strategies. Life Sci. 2016;148:183–93.PubMedCrossRef

28.

Adorno-Cruz V, Kibria G, Liu X, Doherty M, Junk DJ, Guan D, et al. Cancer stem cells: targeting the roots of cancer, seeds of metastasis, and sources of therapy resistance. Cancer Res. 2015;75(6):924–9.PubMedPubMedCentralCrossRef

29.

Gudkov AV, Komarova EA. p53 and the Carcinogenicity of Chronic Inflammation. Cold Spring Harbor Perspectives in Medicine. 2016;6(11). doi:10.1101/cshperspect.a026161.

30.

Grant WB. MM. Role of ultraviolet-B irradiance and vitamin D in reducing risk of cancer. In: Suba Z, editor. Recent avenues to cancer prevention. N.Y.: Nova Science Publishers, Inc.; 2014.

31.

Swami S, Krishnan AV, Feldman D. 1alpha,25-dihydroxyvitamin D3 down-regulates estrogen receptor abundance and suppresses estrogen actions in MCF-7 human breast cancer cells. Clin Cancer Res: An Official Journal of the American Association for Cancer Research. 2000;6(8):3371–9.

32.

Swami S, Raghavachari N, Muller UR, Bao YP, Feldman D. Vitamin D growth inhibition of breast cancer cells: gene expression patterns assessed by cDNA microarray. Breast Cancer Res Treat. 2003;80(1):49–62.PubMedCrossRef

33.

Krishnan AV, Swami S, Feldman D. Vitamin D and breast cancer: inhibition of estrogen synthesis and signaling. J Steroid Biochem Mol Biol. 2010;121(1–2):343–8.PubMedCrossRef

34.

Krishnan AV, Swami S, Peng L, Wang J, Moreno J, Feldman D. Tissue-selective regulation of aromatase expression by calcitriol: implications for breast cancer therapy. Endocrinology. 2010;151(1):32–42. doi:10.1210/en.2009-0855.PubMedCrossRef

35.

Chiang KC, Yeh CN, Chen SC, Shen SC, Hsu JT, Yeh TS, et al. MART-10, a new generation of vitamin D analog, is more potent than 1alpha,25-dihydroxyvitamin D(3) in inhibiting cell proliferation and inducing apoptosis in ER+ MCF-7 breast cancer cells. Evid Based Complement Alternat Med: eCAM. 2012;2012:310872.PubMedPubMedCentralCrossRef

36.

Richards SE, Weierstahl KA, Kelts JL. Vitamin D effect on growth and vitamin D metabolizing enzymes in triple-negative breast cancer. Anticancer Res. 2015;35(2):805–10.PubMed

37.

Mercier T, Chaumontet C, Gaillard-Sanchez I, Martel P, Heberden C. Calcitriol and lexicalcitol (KH1060) inhibit the growth of human breast adenocarcinoma cells by enhancing transforming growth factor-beta production. Biochem Pharmacol. 1996;52(3):505–10.PubMedCrossRef

38.

Yanagisawa J, Yanagi Y, Masuhiro Y, Suzawa M, Watanabe M, Kashiwagi K, et al. Convergence of transforming growth factor-beta and vitamin D signaling pathways on SMAD transcriptional coactivators. Science. 1999;283(5406):1317–21.PubMedCrossRef

39.

Verlinden L, Verstuyf A, Convents R, Marcelis S, Van Camp M, Bouillon R. Action of 1,25(OH)2D3 on the cell cycle genes, cyclin D1, p21 and p27 in MCF-7 cells. Mol Cell Endocrinol. 1998;142(1–2):57–65.PubMedCrossRef

40.

Mantell DJ, Owens PE, Bundred NJ, Mawer EB, Canfield AE. 1 alpha,25-dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo. Circ Res. 2000;87(3):214–20.PubMedCrossRef

41.

Swami S, Krishnan AV, Wang JY, Jensen K, Horst R, Albertelli MA, et al. Dietary vitamin D(3) and 1,25-dihydroxyvitamin D(3) (calcitriol) exhibit equivalent anticancer activity in mouse xenograft models of breast and prostate cancer. Endocrinology. 2012;153(6):2576–87.PubMedPubMedCentralCrossRef

42.

Jeong Y, Swami S, Krishnan AV, Williams JD, Martin S, Horst RL, et al. Inhibition of mouse breast tumor-initiating cells by calcitriol and dietary vitamin D. Mol Cancer Ther. 2015;14(8):1951–61.PubMedPubMedCentralCrossRef

43.

Wahler J, So JY, Cheng LC, Maehr H, Uskokovic M, Suh N. Vitamin D compounds reduce mammosphere formation and decrease expression of putative stem cell markers in breast cancer. J Steroid Biochem Mol Biol. 2015;148:148–55.PubMedCrossRef

44.

Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7.PubMedPubMedCentralCrossRef

45.

Clevers H. At the crossroads of inflammation and cancer. Cell. 2004;118(6):671–4.PubMedCrossRef

46.

Rakoff-Nahoum S. Why cancer and inflammation? Yale J Biol Med. 2006;79(3–4):123–30.PubMed

47.

Omrane I, Benammar-Elgaaied A. The immune microenvironment of the colorectal tumor: involvement of immunity genes and microRNAs belonging to the TH17 pathway. Biochim Biophys Acta. 2015;1856(1):28–38.PubMed

48.

Wang K, Karin M. Tumor-elicited inflammation and colorectal cancer. Adv Cancer Res. 2015;128:173–96.PubMedCrossRef

49.

West AC, Jenkins BJ. Inflammatory and non-inflammatory roles for toll-like receptors in gastrointestinal cancer. Curr Pharm Des. 2015;21(21):2968–77.PubMedCrossRef

50.

Zhao JL, Xiao CX, Guleng B. Immunopathogenesis of colitis-associated cancer in an animal model. Crit Rev Eukaryot Gene Expr. 2015;25(3):245–51.PubMedCrossRef

51.

Bao BY, Yao J, Lee YF. 1alpha, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis. Carcinogenesis. 2006;27(9):1883–93.PubMedCrossRef

52.

Kovalenko PL, Zhang Z, Cui M, Clinton SK, Fleet JC. 1,25 dihydroxyvitamin D-mediated orchestration of anticancer, transcript-level effects in the immortalized, non-transformed prostate epithelial cell line, RWPE1. BMC Genomics. 2010;11:26.PubMedPubMedCentralCrossRef

53.

Kaler P, Augenlicht L, Klampfer L. Macrophage-derived IL-1beta stimulates Wnt signaling and growth of colon cancer cells: a crosstalk interrupted by vitamin D3. Oncogene. 2009;28(44):3892–902.PubMedPubMedCentralCrossRef

54.

Brabletz T, Jung A, Kirchner T. Beta-catenin and the morphogenesis of colorectal cancer. Virchows Arch. 2002;441(1):1–11.PubMedCrossRef

55.

Hadjihannas MV, Bruckner M, Jerchow B, Birchmeier W, Dietmaier W, Behrens J. Aberrant Wnt/beta-catenin signaling can induce chromosomal instability in colon cancer. Proc Natl Acad Sci U S A. 2006;103(28):10747–52.PubMedPubMedCentralCrossRef

56.

Fodde R, Brabletz T. Wnt/beta-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol. 2007;19(2):150–8.PubMedCrossRef

57.

Aguilera O, Pena C, Garcia JM, Larriba MJ, Ordonez-Moran P, Navarro D, et al. The Wnt antagonist DICKKOPF-1 gene is induced by 1alpha,25-dihydroxyvitamin D3 associated to the differentiation of human colon cancer cells. Carcinogenesis. 2007;28(9):1877–84.PubMedCrossRef

58.

Subramaniam N, Leong GM, Cock TA, Flanagan JL, Fong C, Eisman JA, et al. Cross-talk between 1,25-dihydroxyvitamin D3 and transforming growth factor-beta signaling requires binding of VDR and Smad3 proteins to their cognate DNA recognition elements. J Biol Chem. 2001;276(19):15741–6.PubMedCrossRef

59.

Lyakh LA, Sanford M, Chekol S, Young HA, Roberts AB. TGF-beta and vitamin D3 utilize distinct pathways to suppress IL-12 production and modulate rapid differentiation of human monocytes into CD83+ dendritic cells. J Immunol. 2005;174(4):2061–70.PubMedCrossRef

60.

Ruemmele FM, Garnier-Lengline H. Transforming growth factor and intestinal inflammation: the role of nutrition. Nestle Nutr Inst Workshop Ser. 2013;77:91–8.PubMedCrossRef

61.

Chen A, Davis BH, Sitrin MD, Brasitus TA, Bissonnette M. Transforming growth factor-beta 1 signaling contributes to Caco-2 cell growth inhibition induced by 1,25(OH)(2)D(3). Am J Physiol Gastrointest Liver Physiol. 2002;283(4):G864–74.PubMedCrossRef

62.

Chen S, Zhu J, Zuo S, Ma J, Zhang J, Chen G, et al. 1,25(OH)2D3 attenuates TGF-beta1/beta2-induced increased migration and invasion via inhibiting epithelial-mesenchymal transition in colon cancer cells. Biochem Biophys Res Commun. 2015;468(1–2):130–5. doi:10.1016/j.bbrc.2015.10.146.PubMedCrossRef

63.

Tong WM, Hofer H, Ellinger A, Peterlik M, Cross HS. Mechanism of antimitogenic action of vitamin D in human colon carcinoma cells: relevance for suppression of epidermal growth factor-stimulated cell growth. Oncol Res. 1999;11(2):77–84.PubMed

64.

Diaz GD, Paraskeva C, Thomas MG, Binderup L, Hague A. Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: possible implications for prevention and therapy. Cancer Res. 2000;60(8):2304–12.PubMed

65.

Srinivasan M, Parwani AV, Hershberger PA, Lenzner DE, Weissfeld JL. Nuclear vitamin D receptor expression is associated with improved survival in non-small cell lung cancer. J Steroid Biochem Mol Biol. 2011;123(1–2):30–6.PubMedCrossRef

66.

Beer DG, Kardia SL, Huang CC, Giordano TJ, Levin AM, Misek DE, et al. Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med. 2002;8(8):816–24.PubMed

67.

Anderson MG, Nakane M, Ruan X, Kroeger PE, Wu-Wong JR. Expression of VDR and CYP24A1 mRNA in human tumors. Cancer Chemother Pharmacol. 2006;57(2):234–40.PubMedCrossRef

68.

Parise RA, Egorin MJ, Kanterewicz B, Taimi M, Petkovich M, Lew AM, et al. CYP24, the enzyme that catabolizes the antiproliferative agent vitamin D, is increased in lung cancer. Int J Cancer. 2006;119(8):1819–28.PubMedCrossRef

69.

Chen G, Kim SH, King AN, Zhao L, Simpson RU, Christensen PJ, et al. CYP24A1 is an independent prognostic marker of survival in patients with lung adenocarcinoma. Clin Cancer Res : An Official Journal of the American Association for Cancer Research. 2011;17(4):817–26.CrossRef

70.

Zhang Q, Kanterewicz B, Buch S, Petkovich M, Parise R, Beumer J, et al. CYP24 inhibition preserves 1alpha,25-dihydroxyvitamin D(3) anti-proliferative signaling in lung cancer cells. Mol Cell Endocrinol. 2012;355(1):153–61.PubMedPubMedCentralCrossRef

71.

Shay JW, Werbin H, Wright WE. Telomerase assays in the diagnosis and prognosis of cancer. CIBA Found Symp. 1997;211:148–55. discussion 55-9PubMed

72.

Blackburn EH. Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. FEBS Lett. 2005;579(4):859–62.PubMedCrossRef

73.

Kasiappan R, Shen Z, Tse AK, Jinwal U, Tang J, Lungchukiet P, et al. 1,25-dihydroxyvitamin D3 suppresses telomerase expression and human cancer growth through microRNA-498. J Biol Chem. 2012;287(49):41297–309.PubMedPubMedCentralCrossRef

74.

Jiang F, Bao J, Li P, Nicosia SV, Bai W. Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase. J Biol Chem. 2004;279(51):53213–21.PubMedCrossRef

75.

Jiang F, Li P, Fornace Jr AJ, Nicosia SV, Bai W. G2/M arrest by 1,25-dihydroxyvitamin D3 in ovarian cancer cells mediated through the induction of GADD45 via an exonic enhancer. J Biol Chem. 2003;278(48):48030–40.PubMedCrossRef

76.

Ahonen MH, Zhuang YH, Aine R, Ylikomi T, Tuohimaa P. Androgen receptor and vitamin D receptor in human ovarian cancer: growth stimulation and inhibition by ligands. Int J Cancer. 2000;86(1):40–6.PubMedCrossRef

77.

Hummel D, Aggarwal A, Borka K, Bajna E, Kallay E, Horvath HC. The vitamin D system is deregulated in pancreatic diseases. J Steroid Biochem Mol Biol. 2014;144 Pt B:402–409.

78.

Mathew R, Kongara S, Beaudoin B, Karp CM, Bray K, Degenhardt K, et al. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev. 2007;21(11):1367–81.PubMedPubMedCentralCrossRef

79.

Karantza-Wadsworth V, Patel S, Kravchuk O, Chen G, Mathew R, Jin S, et al. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 2007;21(13):1621–35.PubMedPubMedCentralCrossRef

80.

Wang J, Lian H, Zhao Y, Kauss MA, Spindel S. Vitamin D3 induces autophagy of human myeloid leukemia cells. J Biol Chem. 2008;283(37):25596–605.PubMedCrossRef

81.

Albertson DG, Ylstra B, Segraves R, Collins C, Dairkee SH, Kowbel D, et al. Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene. Nat Genet. 2000;25(2):144–6. doi:10.1038/75985.PubMedCrossRef

82.

Mimori K, Tanaka Y, Yoshinaga K, Masuda T, Yamashita K, Okamoto M, et al. Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer. Ann Oncol : Official Journal of the European Society for Medical Oncology / ESMO. 2004;15(2):236–41.CrossRef

83.

Hobaus J, Thiem U, Hummel DM, Kallay E. Role of calcium, vitamin D, and the extrarenal vitamin D hydroxylases in carcinogenesis. Anti Cancer Agents Med Chem. 2013;13(1):20–35.CrossRef

84.

Ikeda N, Uemura H, Ishiguro H, Hori M, Hosaka M, Kyo S, 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. Mol Cancer Ther. 2003;2(8):739–46.PubMed

85.

Hisatake J, Kubota T, Hisatake Y, Uskokovic M, Tomoyasu S, Koeffler HP. 5,6-trans-16-ene-vitamin D3: a new class of potent inhibitors of proliferation of prostate, breast, and myeloid leukemic cells. Cancer Res. 1999;59(16):4023–9.PubMed

86.

Chiang KC, Yeh CN, Hsu JT, Chen LW, Kuo SF, Sun CC, et al. MART-10, a novel vitamin D analog, inhibits head and neck squamous carcinoma cells growth through cell cycle arrest at G0/G1 with upregulation of p21 and p27 and downregulation of telomerase. J Steroid Biochem Mol Biol. 2013;138:427–34.PubMedCrossRef

87.

Blutt SE, McDonnell TJ, Polek TC, Weigel NL. Calcitriol-induced apoptosis in LNCaP cells is blocked by overexpression of Bcl-2. Endocrinology. 2000;141(1):10–7. doi:10.1210/endo.141.1.7289.PubMedCrossRef

88.

Blutt SE, Allegretto EA, Pike JW, Weigel NL. 1,25-dihydroxyvitamin D3 and 9-cis-retinoic acid act synergistically to inhibit the growth of LNCaP prostate cells and cause accumulation of cells in G1. Endocrinology. 1997;138(4):1491–7. doi:10.1210/endo.138.4.5063.PubMedCrossRef

89.

Zhuang SH, Burnstein KL. Antiproliferative effect of 1alpha,25-dihydroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation. Endocrinology. 1998;139(3):1197–207. doi:10.1210/endo.139.3.5770.PubMedCrossRef

90.

Rohan JN, Weigel NL. 1Alpha,25-dihydroxyvitamin D3 reduces c-Myc expression, inhibiting proliferation and causing G1 accumulation in C4-2 prostate cancer cells. Endocrinology. 2009;150(5):2046–54. doi:10.1210/en.2008-1395.PubMedPubMedCentralCrossRef

91.

Washington MN, Kim JS, Weigel NL. 1alpha,25-dihydroxyvitamin D3 inhibits C4-2 prostate cancer cell growth via a retinoblastoma protein (Rb)-independent G1 arrest. Prostate. 2011;71(1):98–110. doi:10.1002/pros.21226.PubMedPubMedCentralCrossRef

92.

Deeb KK, Luo W, Karpf AR, Omilian AR, Bshara W, Tian L, et al. Differential vitamin D 24-hydroxylase/CYP24A1 gene promoter methylation in endothelium from benign and malignant human prostate. Epigenetics. 2011;6(8):994–1000.PubMedPubMedCentralCrossRef

93.

Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44–84. doi:10.1016/j.biocel.2006.07.001.PubMedCrossRef

94.

Bao BY, Ting HJ, Hsu JW, Lee YF. Protective role of 1 alpha, 25-dihydroxyvitamin D3 against oxidative stress in nonmalignant human prostate epithelial cells. Int J Cancer. 2008;122(12):2699–706. doi:10.1002/ijc.23460.PubMedCrossRef

95.

Ben-Shoshan M, Amir S, Dang DT, Dang LH, Weisman Y, Mabjeesh NJ. 1alpha,25-dihydroxyvitamin D3 (calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells. Mol Cancer Ther. 2007;6(4):1433–9. doi:10.1158/1535-7163.MCT-06-0677.PubMedCrossRef

96.

Chung I, Han G, Seshadri M, Gillard BM, Yu WD, Foster BA, et al. Role of vitamin D receptor in the antiproliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo. Cancer Res. 2009;69(3):967–75. doi:10.1158/0008-5472.CAN-08-2307.PubMedPubMedCentralCrossRef

97.

Ray R, Banks M, Abuzahra H, Eddy VJ, Persons KS, Lucia MS, et al. Effect of dietary vitamin D and calcium on the growth of androgen-insensitive human prostate tumor in a murine model. Anticancer Res. 2012;32(3):727–31.PubMedPubMedCentral

98.

Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980;9(3):227–31.PubMedCrossRef

99.

Grant WB. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer. 2002;94(6):1867–75. doi:10.1002/cncr.10427.PubMedCrossRef

100.

Grant WB, Garland CF. The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Anticancer Res. 2006;26(4A):2687–99.PubMed

101.

Lin SW, Wheeler DC, Park Y, Cahoon EK, Hollenbeck AR, Freedman DM, et al. Prospective study of ultraviolet radiation exposure and risk of cancer in the United States. Int J Cancer. 2012;131(6):E1015–23. doi:10.1002/ijc.27619.PubMedPubMedCentralCrossRef

102.

Zamoiski RD, Freedman DM, Linet MS, Kitahara CM, Liu W, Cahoon EK. Prospective study of ultraviolet radiation exposure and risk of breast cancer in the United States. Environ Res. 2016;151:419–27. doi:10.1016/j.envres.2016.08.013.PubMedCrossRef

103.

Grant WB. Re: prospective study of ultraviolet radiation exposure and risk of breast cancer in the United States. Environ Res. 2017;152(1):517–8

104.

Grant WB. 25-hydroxyvitamin D and breast cancer, colorectal cancer, and colorectal adenomas: case-control versus nested case-control studies. Anticancer Res. 2015;35(2):1153–60.PubMed

105.

Oh EY, Ansell C, Nawaz H, Yang CH, Wood PA, Hrushesky WJ. Global breast cancer seasonality. Breast Cancer Res Treat. 2010;123(1):233–43. doi:10.1007/s10549-009-0676-7.PubMedCrossRef

106.

Eliassen AH, Warner ET, Rosner B, Collins LC, Beck AH, Quintana LM, et al. Plasma 25-hydroxyvitamin D and risk of breast cancer in women followed over 20 Years. Cancer Res. 2016;76(18):5423–30. doi:10.1158/0008-5472.CAN-16-0353.PubMedCrossRef

107.

Tretli S, Schwartz GG, Torjesen PA, Robsahm TE. Serum levels of 25-hydroxyvitamin D and survival in Norwegian patients with cancer of breast, colon, lung, and lymphoma: a population-based study. Cancer Causes Control. 2012;23(2):363–70. doi:10.1007/s10552-011-9885-6.PubMedCrossRef

108.

Yao S, Sucheston LE, Millen AE, Johnson CS, Trump DL, Nesline MK, et al. Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study. PLoS One. 2011;6(2):e17251. doi:10.1371/journal.pone.0017251.PubMedPubMedCentralCrossRef

109.

Fedirko V, Torres-Mejia G, Ortega-Olvera C, Biessy C, Angeles-Llerenas A, Lazcano-Ponce E, et al. Serum 25-hydroxyvitamin D and risk of breast cancer: results of a large population-based case-control study in Mexican women. Cancer Causes Control. 2012;23(7):1149–62. doi:10.1007/s10552-012-9984-z.PubMedCrossRef

110.

Thanasitthichai S, Chaiwerawattana A, Prasitthipayong A. Association of Vitamin D Level with Clinicopathological features in breast cancer. Asian Pac J Cancer Prev. 2015;16(12):4881–3.PubMedCrossRef

111.

Haugen J, Chandyo RK, Ulak M, Mathisen M, Basnet S, Brokstad KA, et al. 25-hydroxy-vitamin D concentration is not affected by severe or non-severe pneumonia, or inflammation, in young children. Nutrition. 2017;9(1). doi:10.3390/nu9010052.

112.

Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set. Am J Clin Nutr. 2011;94(4):1144–9. doi:10.3945/ajcn.111.015032.PubMedPubMedCentralCrossRef

113.

IARC. Vitamin D and cancer. Lyon: International agency for research on cancer; 2008.

114.

Ma Y, Zhang P, Wang F, Yang J, Liu Z, Qin H. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. J Clin Oncol : official journal of the American Society of Clinical Oncology. 2011;29(28):3775–82. doi:10.1200/JCO.2011.35.7566.CrossRef

115.

Mohr SB, Gorham ED, Kim J, Hofflich H, Cuomo RE, Garland CF. Could vitamin D sufficiency improve the survival of colorectal cancer patients? J Steroid Biochem Mol Biol. 2015;148:239–44. doi:10.1016/j.jsbmb.2014.12.010.PubMedCrossRef

116.

Zgaga L, Theodoratou E, Farrington SM, Din FV, Ooi LY, Glodzik D, et al. Plasma vitamin D concentration influences survival outcome after a diagnosis of colorectal cancer. J Clin Oncol : official journal of the American Society of Clinical Oncology. 2014;32(23):2430–9. doi:10.1200/JCO.2013.54.5947.CrossRef

117.

Chen GC, Zhang ZL, Wan Z, Wang L, Weber P, Eggersdorfer M, et al. Circulating 25-hydroxyvitamin D and risk of lung cancer: a dose-response meta-analysis. Cancer Causes Control. 2015. doi:10.1007/s10552-015-0665-6.PubMedCentral

118.

Zhang L, Wang S, Che X, Li X. Vitamin D and lung cancer risk: a comprehensive review and meta-analysis. Cell Physiol Biochem. 2015;36(1):299–305. doi:10.1159/000374072.PubMedCrossRef

119.

Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: serum vitamin D and colorectal adenoma risk. Prev Med. 2011;53(1–2):10–6. doi:10.1016/j.ypmed.2011.05.013.PubMedCrossRef

120.

Prescott J, Bertrand KA, Poole EM, Rosner BA, Tworoger SS. Surrogates of long-term vitamin d exposure and ovarian cancer risk in two prospective cohort studies. Cancers (Basel). 2013;5(4):1577–600. doi:10.3390/cancers5041577.CrossRef

121.

Tran B, Jordan SJ, Lucas R, Webb PM, Neale R. Association between ambient ultraviolet radiation and risk of epithelial ovarian cancer. Cancer Prev Res (Phila). 2012;5(11):1330–6. doi:10.1158/1940-6207.CAPR-12-0279.CrossRef

122.

Ong JS, Cuellar-Partida G, Lu Y. Ovarian Cancer Study A, Fasching PA, Hein A et al. Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study. Int J Epidemiol. 2016. doi:10.1093/ije/dyw207.

123.

Wolpin BM, Ng K, Bao Y, Kraft P, Stampfer MJ, Michaud DS, et al. Plasma 25-hydroxyvitamin D and risk of pancreatic cancer. Cancer Epidemiol Biomark Prev : a Publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2012;21(1):82–91. doi:10.1158/1055-9965.EPI-11-0836.CrossRef

124.

Altieri B, Grant WB, Casa SD, Orio F, Pontecorvi A, Colao A, et al. Vitamin D and pancreas: the role of sunshine vitamin in the pathogenesis of diabetes mellitus and pancreatic cancer. Crit Rev Food Sci Nutr. 2016. doi:10.1080/10408398.2015.1136922.

125.

Eryilmaz MK, Mutlu H, Gunduz S, Uysal M, Musri FY, Coskun HS. More sunlight exposure may improve the overall survival in patients with pancreas cancer. J Oncol Sci. 2015;2(2–3):73–6.

126.

Grant WB. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level: implications for meta-analyses and setting vitamin D guidelines. Dermato-endocrinol. 2011;3(3):199–204. doi:10.4161/derm.3.3.15364.CrossRef

127.

Xu Y, Shao X, Yao Y, Xu L, Chang L, Jiang Z, et al. Positive association between circulating 25-hydroxyvitamin D levels and prostate cancer risk: new findings from an updated meta-analysis. J Cancer Res Clin Oncol. 2014;140(9):1465–77. doi:10.1007/s00432-014-1706-3.PubMedCrossRef

128.

Gilbert R, Metcalfe C, Fraser WD, Donovan J, Hamdy F, Neal DE, et al. Associations of circulating 25-hydroxyvitamin D with prostate cancer diagnosis, stage and grade. Int J Cancer. 2012;131(5):1187–96. doi:10.1002/ijc.27327.PubMedCrossRef

129.

Marshall DT, Savage SJ, Garrett-Mayer E, Keane TE, Hollis BW, Horst RL, et al. Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance. J Clin Endocrinol Metab. 2012;97(7):2315–24. doi:10.1210/jc.2012-1451.PubMedPubMedCentralCrossRef

130.

Mondul AM, Weinstein SJ, Moy KA, Mannisto S, Albanes D. Circulating 25-Hydroxyvitamin D and Prostate Cancer Survival. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2016. doi:10.1158/1055–9965.EPI-15-0991.

131.

Brandstedt J, Almquist M, Ulmert D, Manjer J, Malm J. Vitamin D, PTH, and calcium and tumor aggressiveness in prostate cancer: a prospective nested case-control study. Cancer Causes Control. 2016;27(1):69–80. doi:10.1007/s10552-015-0684-3.PubMedCrossRef

132.

Garland C, Shekelle RB, Barrett-Connor E, Criqui MH, Rossof AH, Paul O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet. 1985;1(8424):307–9.PubMedCrossRef

133.

Garland CF, Comstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham ED. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet. 1989;2(8673):1176–8.PubMedCrossRef

134.

Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2011;128(6):1414–24. doi:10.1002/ijc.25439.PubMedCrossRef

135.

Rebel H, der Spek CD, Salvatori D, van Leeuwen JP, Robanus-Maandag EC, de Gruijl FR. UV exposure inhibits intestinal tumor growth and progression to malignancy in intestine-specific Apc mutant mice kept on low vitamin D diet. Int J Cancer. 2015;136(2):271–7. doi:10.1002/ijc.29002.PubMedCrossRef

136.

Donneyong MM, Taylor KC, Kerber RA, Hornung CA, Scragg R. Is outdoor recreational activity an independent predictor of cardiovascular disease mortality - NHANES III? Nutr Metab Cardiovasc Dis. 2016;26(8):735–42. doi:10.1016/j.numecd.2016.02.008.PubMedCrossRef

137.

Giovannucci E, Liu Y, Willett WC. Cancer incidence and mortality and vitamin D in black and white male health professionals. Clin Cancer Res: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2006;15(12):2467–72. doi:10.1158/1055-9965.EPI-06-0357.

138.

Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85(6):1586–91.PubMed

139.

Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev. 2014;72(1):48–54. doi:10.1111/nure.12090.PubMedCrossRef

140.

Lappe J, Travers-Gustafon D, Garland C, Heaney R, Recker R, Watson P. Vitamin D3 and calcium supplementation significantly decreases cancer risk in older women. American Public Health Association 2016 meeting; October 31, 2016; Denver, Colorado 2016.

141.

Milczarek M, Psurski M, Kutner A, Wietrzyk J. Vitamin D analogs enhance the anticancer activity of 5-fluorouracil in an in vivo mouse colon cancer model. BMC Cancer. 2013;13:294. doi:10.1186/1471-2407-13-294.PubMedPubMedCentralCrossRef

142.

Milczarek M, Rosinska S, Psurski M, Maciejewska M, Kutner A, Wietrzyk J. Combined colonic cancer treatment with vitamin D analogs and irinotecan or oxaliplatin. Anticancer Res. 2013;33(2):433–44.PubMed

143.

Milczarek M, Filip-Psurska B, Swietnicki W, Kutner A, Wietrzyk J. Vitamin D analogs combined with 5-fluorouracil in human HT-29 colon cancer treatment. Oncol Rep. 2014;32(2):491–504. doi:10.3892/or.2014.3247.PubMedPubMedCentral

144.

Hershberger PA, Yu WD, Modzelewski RA, Rueger RM, Johnson CS, Trump DL. Calcitriol (1,25-dihydroxycholecalciferol) enhances paclitaxel antitumor activity in vitro and in vivo and accelerates paclitaxel-induced apoptosis. Clin Cancer Res : An Official Journal of the American Association for Cancer Research. 2001;7(4):1043–51.

145.

Koshizuka K, Koike M, Asou H, Cho SK, Stephen T, Rude RK, et al. Combined effect of vitamin D3 analogs and paclitaxel on the growth of MCF-7 breast cancer cells in vivo. Breast Cancer Res Treat. 1999;53(2):113–20.PubMedCrossRef

146.

Zeichner SB, Koru-Sengul T, Shah N, Liu Q, Markward NJ, Montero AJ, et al. Improved clinical outcomes associated with vitamin D supplementation during adjuvant chemotherapy in patients with HER2+ nonmetastatic breast cancer. Clin Breast Cancer. 2015;15(1):e1–11. doi:10.1016/j.clbc.2014.08.001.PubMedCrossRef

147.

Ma Y, Yu WD, Hershberger PA, Flynn G, Kong RX, Trump DL, et al. 1alpha,25-dihydroxyvitamin D3 potentiates cisplatin antitumor activity by p73 induction in a squamous cell carcinoma model. Mol Cancer Ther. 2008;7(9):3047–55. doi:10.1158/1535-7163.MCT-08-0243.PubMedPubMedCentralCrossRef

148.

Hershberger PA, McGuire TF, Yu WD, Zuhowski EG, Schellens JH, Egorin MJ, et al. Cisplatin potentiates 1,25-dihydroxyvitamin D3-induced apoptosis in association with increased mitogen-activated protein kinase kinase kinase 1 (MEKK-1) expression. Mol Cancer Ther. 2002;1(10):821–9.PubMed

149.

Refaat B, El-Shemi AG, Kensara OA, Mohamed AM, Idris S, Ahmad J, et al. Vitamin D3 enhances the tumouricidal effects of 5-fluorouracil through multipathway mechanisms in azoxymethane rat model of colon cancer. J Exp Clin Cancer Res : CR. 2015;34:71. doi:10.1186/s13046-015-0187-9.PubMedPubMedCentralCrossRef

150.

McGuire TF, Trump DL, Johnson CS. Vitamin D(3)-induced apoptosis of murine squamous cell carcinoma cells. Selective induction of caspase-dependent MEK cleavage and up-regulation of MEKK-1. J Biol Chem. 2001;276(28):26365–73. doi:10.1074/jbc.M010101200.PubMedCrossRef

Title: The roles of UVB and vitamin D in reducing risk of cancer incidence and mortality: A review of the epidemiology, clinical trials, and mechanisms
Authors: Meis Moukayed
William B. Grant
Publication date: 01-06-2017
Publisher: Springer US
Published in: Reviews in Endocrine and Metabolic Disorders / Issue 2/2017
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI: https://doi.org/10.1007/s11154-017-9415-2

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2017

Vitamin D and autism, what’s new?

Vitamin D, sub-inflammation and insulin resistance. A window on a potential role for the interaction between bone and glucose metabolism

Low vitamin D status and obesity: Role of nutritionist

Low serum vitamin D-status, air pollution and obesity: A dangerous liaison

Vitamin D and its role in psoriasis: An overview of the dermatologist and nutritionist

New light on an old vitamin: The role of the sunshine vitamin D in chronic disease

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage