Skip to main content
SpringerLink
Log in

Vitamin D and Gastrointestinal Cancers: A Narrative Review

  • Review
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Calcitriol (1,25(OH)2D3) performs various activities throughout the body. Although low serum 25-hydroxyvitamin D [25(OH)D] levels are associated with several disease processes such as risk of fractures and falls, hypertension, cardiovascular disease, and diabetes mellitus, recent evidence attests that this important hormone also regulates several cellular pathways involved in cancer development and progression. Calcitriol modulates several genes controlling gut physiology and calcium homeostasis and also maintains the integrity of epithelial barriers, regulates the absorption of phosphate and calcium, and modulates host defense against pathogens and inflammatory response by interplaying with several types of secretory and immune cells. Vitamin D deficiency is significantly related to increased risk of developing certain types of cancer. This deficiency can be prevented by vitamin D supplementation which is both economical and safe. This can lower the risk of developing cancer and also improve the prognosis of patients with gastrointestinal malignancy, but epidemiological data remain inconsistent. Several retrospective observational studies have demonstrated the benefits of vitamin D supplementation, but a few randomized controlled trials have not seemingly supported the beneficial role of vitamin D supplementation in gastrointestinal cancers. Therefore, in this literature review, we aimed to examine the possible role of vitamin D in gastrointestinal malignancies, including gastric, esophageal, pancreatic, hepatic, and colorectal cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79:362–371.

    Article  CAS  PubMed  Google Scholar 

  2. Fleet JC. Molecular actions of vitamin D contributing to cancer prevention. Mol Asp Med. 2008;29:388–396.

    Article  CAS  Google Scholar 

  3. Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in the United States and Canada: current status and data needs. Am J Clin Nutr. 2004;80:1710S–1716S.

    Article  CAS  PubMed  Google Scholar 

  4. White P, Cooke N. The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab. 2000;11:320–327.

    Article  CAS  Google Scholar 

  5. Jacobs ET, Van Pelt C, Forster RE, et al. CYP24A1 and CYP27B1 polymorphisms modulate vitamin D metabolism in colon cancer cells. Cancer Res. 2013;73:2563–2573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Dudenkov DV, Yawn BP, Oberhelman SS, et al. Changing incidence of serum 25-hydroxyvitamin D values above 50 ng/mL: a 10-year population-based study. Mayo Clin Proc. 2015;90:577–586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rooney MR, Harnack L, Michos ED, Ogilvie RP, Sempos CT, Lutsey PL. Trends in use of high-dose vitamin D supplements exceeding 1000 or 4000 international units daily, 1999–2014. JAMA. 2017;317:2448–2450.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zehnder D, Bland R, Williams MC, et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. 2001;86:888–894.

    CAS  PubMed  Google Scholar 

  9. Ingles SA, Ross RK, Yu MC, et al. Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor. J Natl Cancer Inst. 1997;89:166–170.

    Article  CAS  PubMed  Google Scholar 

  10. Haussler MR, Mangelsdorf DJ, Komm BS, et al. Molecular biology of the vitamin D hormone. Recent Prog Horm Res. 1988;44:263–305.

    CAS  PubMed  Google Scholar 

  11. Taymans SE, Pack S, Pak E, et al. The human vitamin D receptor gene (VDR) is localized to region 12cen-q12 by fluorescent in situ hybridization and radiation hybrid mapping: genetic and physical VDR map. J Bone Miner Res. 1999;14:1163–1166.

    Article  CAS  PubMed  Google Scholar 

  12. Zmuda JM, Cauley JA, Ferrell RE. Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev. 2000;22:203–217.

    Article  CAS  PubMed  Google Scholar 

  13. Crofts LA, Hancock MS, Morrison NA, Eisman JA. Multiple promoters direct the tissue-specific expression of novel N-terminal variant human vitamin D receptor gene transcripts. Proc Natl Acad Sci USA. 1998;95:10529–10534.

    Article  CAS  PubMed  Google Scholar 

  14. Rai V, Abdo J, Agrawal S, Agrawal DK. Vitamin D receptor polymorphism and cancer: an update. Anticancer Res. 2017;37:3991–4003.

    CAS  PubMed  Google Scholar 

  15. Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 2006;92:4–8.

    Article  CAS  PubMed  Google Scholar 

  16. Fleet JC, DeSmet M, Johnson R, Li Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J. 2012;441:61–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Picotto G, Liaudat AC, Bohl L, Tolosa de Talamoni N. Molecular aspects of vitamin D anticancer activity. Cancer Invest. 2012;30:604–614.

    Article  CAS  PubMed  Google Scholar 

  18. Davis CD. Vitamin D and cancer: current dilemmas and future research needs. Am J Clin Nutr. 2008;88:565S–569S.

    Article  CAS  PubMed  Google Scholar 

  19. Lamprecht SA, Lipkin M. Cellular mechanisms of calcium and vitamin D in the inhibition of colorectal carcinogenesis. Ann N Y Acad Sci. 2001;952:73–87.

    Article  CAS  PubMed  Google Scholar 

  20. Chung I, Han G, Seshadri M, 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;69:967–975.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Reichrath J, Rafi L, Rech M, et al. Analysis of the vitamin D system in cutaneous squamous cell carcinomas. J Cutan Pathol. 2004;31:224–231.

    Article  PubMed  Google Scholar 

  22. Hansen CM, Binderup L, Hamberg KJ, Carlberg C. Vitamin D and cancer: effects of 1,25(OH)2D3 and its analogs on growth control and tumorigenesis. Front Biosci. 2001;6:D820–D848.

    CAS  PubMed  Google Scholar 

  23. Osborne JE, Hutchinson PE. Vitamin D and systemic cancer: is this relevant to malignant melanoma? Br J Dermatol. 2002;147:197–213.

    Article  CAS  PubMed  Google Scholar 

  24. Lamprecht SA, Lipkin M. Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Nat Rev Cancer. 2003;3:601–614.

    Article  CAS  PubMed  Google Scholar 

  25. Taylor JA, Hirvonen A, Watson M, Pittman G, Mohler JL, Bell DA. Association of prostate cancer with vitamin D receptor gene polymorphism. Cancer Res. 1996;56:4108–4110.

    CAS  PubMed  Google Scholar 

  26. Curran JE, Vaughan T, Lea RA, Weinstein SR, Morrison NA, Griffiths LR. Association of A vitamin D receptor polymorphism with sporadic breast cancer development. Int J Cancer. 1999;83:723–726.

    Article  CAS  PubMed  Google Scholar 

  27. Fetahu IS, Hummel DM, Manhardt T, Aggarwal A, Baumgartner-Parzer S, Kállay E. Regulation of the calcium-sensing receptor expression by 1,25-dihydroxyvitamin D3, interleukin-6, and tumor necrosis factor alpha in colon cancer cells. J Steroid Biochem Mol Biol. 2014;144:228–231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Canaff L, Hendy GN. Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D. J Biol Chem. 2002;277:30337–30350.

    Article  CAS  PubMed  Google Scholar 

  29. Garland CF, Garland FC, Gorham ED, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96:252–261.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wu K, Feskanich D, Fuchs CS, Willett WC, Hollis BW, Giovannucci EL. A nested case–control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. J Natl Cancer Inst. 2007;99:1120–1129.

    Article  CAS  PubMed  Google Scholar 

  31. Wactawski-Wende J, Kotchen JM, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006;354:684–696.

    Article  CAS  PubMed  Google Scholar 

  32. 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;2:1176–1178.

    Article  CAS  PubMed  Google Scholar 

  33. Engel P, Fagherazzi G, Boutten A, et al. Serum 25(OH) vitamin D and risk of breast cancer: a nested case–control study from the French E3N cohort. Cancer Epidemiol Biomark Prev. 2010;19:2341–2350.

    Article  CAS  Google Scholar 

  34. Skinner HG, Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiol Biomark Prev. 2006;15:1688–1695.

    Article  CAS  Google Scholar 

  35. Gao J, Wei W, Wang G, Zhou H, Fu Y, Liu N. Circulating vitamin D concentration and risk of prostate cancer: a dose-response meta-analysis of prospective studies. Ther Clin Risk Manag. 2018;14:95–104.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Larriba MJ, Ordóñez-Morán P, Chicote I, et al. Vitamin D receptor deficiency enhances Wnt/β-catenin signaling and tumor burden in colon cancer. PLoS ONE. 2011;6:e23524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Llor X, Jacoby RF, Teng BB, Davidson NO, Sitrin MD, Brasitus TA. K-ras mutations in 1,2-dimethylhydrazine-induced colonic tumors: effects of supplemental dietary calcium and vitamin D deficiency. Cancer Res. 1991;51:4305–4309.

    CAS  PubMed  Google Scholar 

  38. Sitrin MD, Halline AG, Abrahams C, Brasitus TA. Dietary calcium and vitamin D modulate 1,2-dimethylhydrazine-induced colonic carcinogenesis in the rat. Cancer Res. 1991;51:5608–5613.

    CAS  PubMed  Google Scholar 

  39. 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;26:2687–2699.

    CAS  PubMed  Google Scholar 

  40. Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980;9:227–231.

    Article  CAS  PubMed  Google Scholar 

  41. Neale RE, Youlden DR, Krnjacki L, Kimlin MG, van der Pols JC. Latitude variation in pancreatic cancer mortality in Australia. Pancreas. 2009;38:387–390.

    Article  PubMed  Google Scholar 

  42. Tran B, Lucas R, Kimlin M, Whiteman D, Neale R, Study AC. Association between ambient ultraviolet radiation and risk of esophageal cancer. Am J Gastroenterol. 2012;107:1803–1813.

    Article  PubMed  Google Scholar 

  43. 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;136:271–277.

    Article  CAS  PubMed  Google Scholar 

  44. Makarova AM, Frascari F, Davari P, et al. Ultraviolet radiation inhibits mammary carcinogenesis in an ER-negative murine model by a mechanism independent of vitamin D. Cancer Prev Res (Phila). 2018;11:383–392.

    Article  CAS  Google Scholar 

  45. Polednak AP. Trends in survival for both histologic types of esophageal cancer in US surveillance, epidemiology and end results areas. Int J Cancer. 2003;105:98–100.

    Article  CAS  PubMed  Google Scholar 

  46. Chang CK, Mulholland HG, Cantwell MM, et al. Vitamin D receptor gene variants and esophageal adenocarcinoma risk: a population-based case–control study. J Gastrointest Cancer. 2012;43:512–517.

    Article  CAS  PubMed  Google Scholar 

  47. Chen PT, Hsieh CC, Wu CT, et al. 1α,25-dihydroxyvitamin D3 inhibits esophageal squamous cell carcinoma progression by reducing IL6 signaling. Mol Cancer Ther. 2015;14:1365–1375.

    Article  CAS  PubMed  Google Scholar 

  48. Gan X, Chen B, Shen Z, et al. High GPX1 expression promotes esophageal squamous cell carcinoma invasion, migration, proliferation and cisplatin-resistance but can be reduced by vitamin D. Int J Clin Exp Med. 2014;7:2530–2540.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Trowbridge R, Sharma P, Hunter WJ, Agrawal DK. Vitamin D receptor expression and neoadjuvant therapy in esophageal adenocarcinoma. Exp Mol Pathol. 2012;93:147–153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mulholland HG, Murray LJ, Anderson LA, Cantwell MM, group Fs. Vitamin D, calcium and dairy intake, and risk of oesophageal adenocarcinoma and its precursor conditions. Br J Nutr. 2011;106:732–741.

    Article  CAS  PubMed  Google Scholar 

  51. Launoy G, Milan C, Day NE, Pienkowski MP, Gignoux M, Faivre J. Diet and squamous-cell cancer of the oesophagus: a French multicentre case–control study. Int J Cancer. 1998;76:7–12.

    Article  CAS  PubMed  Google Scholar 

  52. Giovannucci E, Liu Y, Rimm EB, et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006;98:451–459.

    Article  CAS  PubMed  Google Scholar 

  53. Wang L, Wang C, Wang J, Huang X, Cheng Y. Longitudinal, observational study on associations between postoperative nutritional vitamin D supplementation and clinical outcomes in esophageal cancer patients undergoing esophagectomy. Sci Rep. 2016;6:38962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Abnet CC, Chen Y, Chow WH, et al. Circulating 25-hydroxyvitamin D and risk of esophageal and gastric cancer: cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. 2010;172:94–106.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Fanidi A, Muller DC, Midttun Ø, et al. Circulating vitamin D in relation to cancer incidence and survival of the head and neck and oesophagus in the EPIC cohort. Sci Rep. 2016;6:36017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Thota PN, Kistangari G, Singh P, et al. Serum 25-hydroxyvitamin D levels and the risk of dysplasia and esophageal adenocarcinoma in patients with Barrett’s esophagus. Dig Dis Sci. 2016;61:247–254. https://doi.org/10.1007/s10620-015-3823-5.

    Article  CAS  PubMed  Google Scholar 

  57. Abnet CC, Chen W, Dawsey SM, et al. Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. Cancer Epidemiol Biomark Prev. 2007;16:1889–1893.

    Article  CAS  Google Scholar 

  58. Trowbridge R, Mittal SK, Sharma P, Hunter WJ, Agrawal DK. Vitamin D receptor expression in the mucosal tissue at the gastroesophageal junction. Exp Mol Pathol. 2012;93:246–249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zgaga L, O’Sullivan F, Cantwell MM, Murray LJ, Thota PN, Coleman HG. Markers of vitamin D exposure and esophageal cancer risk: a systematic review and meta-analysis. Cancer Epidemiol Biomark Prev. 2016;25:877–886.

    Article  CAS  Google Scholar 

  60. Risch HA, Jain M, Choi NW, et al. Dietary factors and the incidence of cancer of the stomach. Am J Epidemiol. 1985;122:947–959.

    Article  CAS  PubMed  Google Scholar 

  61. Nomura A, Grove JS, Stemmermann GN, Severson RK. Cigarette smoking and stomach cancer. Cancer Res. 1990;50:7084.

    CAS  PubMed  Google Scholar 

  62. Scartozzi M, Galizia E, Verdecchia L, et al. Chemotherapy for advanced gastric cancer: across the years for a standard of care. Expert Opin Pharmacother. 2007;8:797–808.

    Article  CAS  PubMed  Google Scholar 

  63. Park MR, Lee JH, Park MS, et al. Suppressive effect of 19-nor-1α-25-dihydroxyvitamin D2 on gastric cancer cells and peritoneal metastasis model. J Korean Med Sci. 2012;27:1037–1043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Anderson MG, Nakane M, Ruan X, Kroeger PE, Wu-Wong JR. Expression of VDR and CYP24A1 mRNA in human tumors. Cancer Chemother Pharmacol. 2006;57:234–240.

    Article  CAS  PubMed  Google Scholar 

  65. Bao A, Li Y, Tong Y, Zheng H, Wu W, Wei C. Tumor-suppressive effects of 1, 25-dihydroxyvitamin D3 in gastric cancer cells. Hepatogastroenterology. 2013;60:943–948.

    CAS  PubMed  Google Scholar 

  66. Baek S, Lee YS, Shim HE, et al. Vitamin D3 regulates cell viability in gastric cancer and cholangiocarcinoma. Anat Cell Biol. 2011;44:204–209.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Ikezaki S, Nishikawa A, Furukawa F, et al. Chemopreventive effects of 24R,25-dihydroxyvitamin D3, a vitamin D3 derivative, on glandular stomach carcinogenesis induced in rats by N-methyl-N′-nitro-N-nitrosoguanidine and sodium chloride. Cancer Res. 1996;56:2767–2770.

    CAS  PubMed  Google Scholar 

  68. Ren C, Qiu MZ, Wang DS, et al. Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer. J Transl Med. 2012;10:16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Khayatzadeh S, Feizi A, Saneei P, Esmaillzadeh A. Vitamin D intake, serum Vitamin D levels, and risk of gastric cancer: a systematic review and meta-analysis. J Res Med Sci. 2015;20:790–796.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–2576.

    Article  CAS  PubMed  Google Scholar 

  71. Kitson MT, Roberts SK. D-livering the message: the importance of vitamin D status in chronic liver disease. J Hepatol. 2012;57:897–909.

    Article  CAS  PubMed  Google Scholar 

  72. Imawari M, Akanuma Y, Itakura H, Muto Y, Kosaka K, Goodman DS. The effects of diseases of the liver on serum 25-hydroxyvitamin D and on the serum binding protein for vitamin D and its metabolites. J Lab Clin Med. 1979;93:171–180.

    CAS  PubMed  Google Scholar 

  73. Horvath E, Lakatos P, Balla B, et al. Marked increase of CYP24A1 mRNA level in hepatocellular carcinoma cell lines following vitamin D administration. Anticancer Res. 2012;32:4791–4796.

    CAS  PubMed  Google Scholar 

  74. Kennedy L, Baker K, Hodges K, et al. Dysregulation of vitamin D3 synthesis leads to enhanced cholangiocarcinoma growth. Dig Liver Dis. 2013;45:316–322.

    Article  CAS  PubMed  Google Scholar 

  75. Hammad LN, Abdelraouf SM, Hassanein FS, Mohamed WA, Schaalan MF. Circulating IL-6, IL-17 and vitamin D in hepatocellular carcinoma: potential biomarkers for a more favorable prognosis? J Immunotoxicol. 2013;10:380–386.

    Article  CAS  PubMed  Google Scholar 

  76. Ghous Z, Akhter J, Pourgholami MH, Morris DL. Inhibition of hepatocellular cancer by EB1089: in vitro and in vive study. Anticancer Res. 2008;28:3757–3761.

    CAS  PubMed  Google Scholar 

  77. Pourgholami MH, Akhter J, Lu Y, Morris DL. In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3. Cancer Lett. 2000;151:97–102.

    Article  CAS  PubMed  Google Scholar 

  78. Chiang KC, Yen CL, Yeh CN, et al. Hepatocellular carcinoma cells express 25(OH)D-1α-hydroxylase and are able to convert 25(OH)D to 1α,25(OH)2D, leading to the 25(OH)D-induced growth inhibition. J Steroid Biochem Mol Biol. 2015;154:47–52.

    Article  CAS  PubMed  Google Scholar 

  79. Chen J, Katz LH, Muñoz NM, et al. Vitamin D deficiency promotes liver tumor growth in transforming growth factor-β/Smad3-deficient mice through Wnt and toll-like receptor 7 pathway modulation. Sci Rep. 2016;6:30217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Fedirko V, Duarte-Salles T, Bamia C, et al. Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case–control study. Hepatology. 2014;60:1222–1230.

    Article  CAS  PubMed  Google Scholar 

  81. Finkelmeier F, Kronenberger B, Köberle V, et al. Severe 25-hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma—a prospective cohort study. Aliment Pharmacol Ther. 2014;39:1204–1212.

    Article  CAS  PubMed  Google Scholar 

  82. Seubwai W, Wongkham C, Puapairoj A, Khuntikeo N, Wongkham S. Overexpression of vitamin D receptor indicates a good prognosis for cholangiocarcinoma: implications for therapeutics. Cancer. 2007;109:2497–2505.

    Article  CAS  PubMed  Google Scholar 

  83. Albrechtsson E, Jonsson T, Möller S, Höglund M, Ohlsson B, Axelson J. Vitamin D receptor is expressed in pancreatic cancer cells and a vitamin D3 analogue decreases cell number. Pancreatology. 2003;3:41–46.

    Article  CAS  PubMed  Google Scholar 

  84. Kawa S, Yoshizawa K, Tokoo M, et al. Inhibitory effect of 220-oxa-1,25-dihydroxyvitamin D3 on the proliferation of pancreatic cancer cell lines. Gastroenterology. 1996;110:1605–1613.

    Article  CAS  PubMed  Google Scholar 

  85. Ohlsson B, Albrechtsson E, Axelson J. Vitamins A and D but not E and K decreased the cell number in human pancreatic cancer cell lines. Scand J Gastroenterol. 2004;39:882–885.

    Article  CAS  PubMed  Google Scholar 

  86. Schwartz GG, Eads D, Rao A, et al. Pancreatic cancer cells express 25-hydroxyvitamin D-1 alpha-hydroxylase and their proliferation is inhibited by the prohormone 25-hydroxyvitamin D3. Carcinogenesis. 2004;25:1015–1026.

    Article  CAS  PubMed  Google Scholar 

  87. Cho M, Peddi PF, Ding K, et al. Vitamin D deficiency and prognostics among patients with pancreatic adenocarcinoma. J Transl Med. 2013;11:206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Piper MR, Freedman DM, Robien K, et al. Vitamin D-binding protein and pancreatic cancer: a nested case–control study. Am J Clin Nutr. 2015;101:1206–1215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Grant WB, Karras SN, Bischoff-Ferrari HA, et al. Do studies reporting ‘U’-shaped serum 25-hydroxyvitamin D-health outcome relationships reflect adverse effects? Dermatoendocrinology. 2016;8:e1187349.

    Article  CAS  Google Scholar 

  90. 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. Dermatoendocrinology. 2011;3:199–204.

    Article  CAS  Google Scholar 

  91. Grant WB. 25-hydroxyvitamin D and breast cancer, colorectal cancer, and colorectal adenomas: case–control versus nested case–control studies. Anticancer Res. 2015;35:1153–1160.

    CAS  PubMed  Google Scholar 

  92. Grant WB. Effect of follow-up time on the relation between prediagnostic serum 25-hydroxyvitamin D and all-cause mortality rate. Dermatoendocrinology. 2012;4:198–202.

    Article  CAS  Google Scholar 

  93. Yu WD, Ma Y, Flynn G, et al. Calcitriol enhances gemcitabine anti-tumor activity in vitro and in vivo by promoting apoptosis in a human pancreatic carcinoma model system. Cell Cycle. 2010;9:3022–3029.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Stolzenberg-Solomon RZ, Graubard BI, et al. Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA. 2005;294:2872–2878.

    Article  CAS  PubMed  Google Scholar 

  95. Ahmad S, Chowdhury TA, Boucher BJ. Diabetes and cancer: could vitamin D provide the link? J Diabetes Complicat. 2013;27:184–190.

    Article  PubMed  Google Scholar 

  96. Brüggemann LW, Queiroz KC, Zamani K, van Straaten A, Spek CA, Bijlsma MF. Assessing the efficacy of the hedgehog pathway inhibitor vitamin D3 in a murine xenograft model for pancreatic cancer. Cancer Biol Ther. 2010;10:79–88.

    Article  CAS  PubMed  Google Scholar 

  97. Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–781.

    Article  CAS  Google Scholar 

  98. Heidelbaugh JJ, Tortorello M. The adult well male examination. Am Fam Phys. 2012;85:964–971.

    Google Scholar 

  99. Whitlock EP, Lin JS, Liles E, Beil TL, Fu R. Screening for colorectal cancer: a targeted, updated systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149:638–658.

    Article  PubMed  Google Scholar 

  100. Jacobs ET, Hibler EA, Lance P, Sardo CL, Jurutka PW. Association between circulating concentrations of 25(OH)D and colorectal adenoma: a pooled analysis. Int J Cancer. 2013;133:2980–2988.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Freedman DM, Looker AC, Chang SC, Graubard BI. Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst. 2007;99:1594–1602.

    Article  CAS  PubMed  Google Scholar 

  102. Wei MY, Garland CF, Gorham ED, Mohr SB, Giovannucci E. Vitamin D and prevention of colorectal adenoma: a meta-analysis. Cancer Epidemiol Biomark Prev. 2008;17:2958–2969.

    Article  CAS  Google Scholar 

  103. 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. 2011;29:3775–3782.

    Article  CAS  PubMed  Google Scholar 

  104. Gandini S, Boniol M, Haukka J, 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;128:1414–1424.

    Article  CAS  PubMed  Google Scholar 

  105. Gorham ED, Garland CF, Garland FC, et al. Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med. 2007;32:210–216.

    Article  PubMed  Google Scholar 

  106. Kaler P, Galea V, Augenlicht L, Klampfer L. Tumor associated macrophages protect colon cancer cells from TRAIL-induced apoptosis through IL-1beta-dependent stabilization of Snail in tumor cells. PLoS ONE. 2010;5:e11700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Horváth HC, Lakatos P, Kósa JP, et al. The candidate oncogene CYP24A1: a potential biomarker for colorectal tumorigenesis. J Histochem Cytochem. 2010;58:277–285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Kure S, Nosho K, Baba Y, et al. Vitamin D receptor expression is associated with PIK3CA and KRAS mutations in colorectal cancer. Cancer Epidemiol Biomark Prev. 2009;18:2765–2772.

    Article  CAS  Google Scholar 

  109. Klampfer L. Vitamin D and colon cancer. World J Gastrointest Oncol. 2014;6:430–437.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Aggarwal A, Höbaus J, Tennakoon S, et al. Active vitamin D potentiates the anti-neoplastic effects of calcium in the colon: a cross talk through the calcium-sensing receptor. J Steroid Biochem Mol Biol. 2016;155:231–238.

    Article  CAS  PubMed  Google Scholar 

  111. Bises G, Kállay E, Weiland T, et al. 25-hydroxyvitamin D3-1alpha-hydroxylase expression in normal and malignant human colon. J Histochem Cytochem. 2004;52:985–989.

    Article  CAS  PubMed  Google Scholar 

  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;94:1144–1149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Baron JA, Barry EL, Mott LA, et al. A trial of calcium and vitamin D for the prevention of colorectal adenomas. N Engl J Med. 2015;373:1519–1530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Click B, Pinsky PF, Hickey T, Doroudi M, Schoen RE. Association of colonoscopy adenoma findings with long-term colorectal cancer incidence. JAMA. 2018;319:2021–2031.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Barry EL, Peacock JL, Rees JR, et al. Vitamin D receptor genotype, vitamin D3 supplementation, and risk of colorectal adenomas: a randomized clinical trial. JAMA Oncol. 2017;3:628–635.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Lappe J, Watson P, Travers-Gustafson D, et al. Effect of vitamin D and calcium supplementation on cancer incidence in older women: a randomized clinical trial. JAMA. 2017;317:1234–1243.

    Article  CAS  PubMed  Google Scholar 

  117. Crowe FL, Steur M, Allen NE, Appleby PN, Travis RC, Key TJ. Plasma concentrations of 25-hydroxyvitamin D in meat eaters, fish eaters, vegetarians and vegans: results from the EPIC–Oxford study. Public Health Nutr. 2011;14:340–346.

    Article  PubMed  Google Scholar 

  118. Yang J, Yu J. The association of diet, gut microbiota and colorectal cancer: what we eat may imply what we get. Protein Cell. 2018;9:474–487.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Aune D, De Stefani E, Ronco A, et al. Meat consumption and cancer risk: a case–control study in Uruguay. Asian Pac J Cancer Prev. 2009;10:429–436.

    PubMed  Google Scholar 

  120. Campbell PT, Patel AV, Newton CC, Jacobs EJ, Gapstur SM. Associations of recreational physical activity and leisure time spent sitting with colorectal cancer survival. J Clin Oncol. 2013;31:876–885.

    Article  PubMed  Google Scholar 

  121. World Cancer Research Fund/American Institute for Cancer Research. Continuous update project report. Food, nutrition, physical activity, and the prevention of colorectal cancer. 2011.

  122. Sanchis-Gomar F, Lucia A, Yvert T, et al. Physical inactivity and low fitness deserve more attention to alter cancer risk and prognosis. Cancer Prev Res. 2015;8:105–110.

    Article  Google Scholar 

  123. Grant WB, Boucher BJ. Randomized controlled trials of vitamin D and cancer incidence: a modeling study. PLoS ONE. 2017;12:e0176448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev. 2014;72:48–54.

    Article  PubMed  Google Scholar 

  125. Corey KE, Zheng H, Mendez-Navarro J, et al. Serum vitamin D levels are not predictive of the progression of chronic liver disease in hepatitis C patients with advanced fibrosis. PLoS ONE. 2012;7:e27144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Hartman TJ, Albert PS, Snyder K, et al. The association of calcium and vitamin D with risk of colorectal adenomas. J Nutr. 2005;135:252–259.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Avi Levin and Giuseppe Lippi: Equal senior contribution.

Authors and Affiliations

  1. Mercer University School of Medicine, 707 Pine St, Macon, GA, 31201, USA

    Hemant Goyal

  2. University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA

    Abhilash Perisetti & M. Rubayat Rahman

  3. Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA

    Avi Levin

  4. Section of Clinical Biochemistry, University of Verona, Verona, Italy

    Giuseppe Lippi

Authors
  1. Hemant Goyal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abhilash Perisetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Rubayat Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Avi Levin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giuseppe Lippi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hemant Goyal.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical statement

This manuscript writing and submission is in compliance with the DDS Journal guidelines. This manuscript, as submitted or its essence in another version, is not under consideration for publication elsewhere and will not be published elsewhere while under consideration by Digestive Diseases and Sciences. All authors have made substantive contributions to the study, and all authors endorse the data and conclusions.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Goyal, H., Perisetti, A., Rahman, M.R. et al. Vitamin D and Gastrointestinal Cancers: A Narrative Review. Dig Dis Sci 64, 1098–1109 (2019). https://doi.org/10.1007/s10620-018-5400-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-018-5400-1

Keywords

Search

Navigation