Cancer prevention starts with 30 ng of Vitamin D – Sept 2024

---

Vitamin D supplementation in cancer prevention and the management of cancer therapy

Neoplasma Vol.71, No.4, p. 307–318, 2024 doi:10.4149/neo_2024_240531N240
adislav Klena, Kristina Galvankova, Adela Penesova, Olga Krizanova

Vitamin D is an important steroid hormone that exerts immunomodulatory actions, controls calcium and phosphate homeostasis, and significantly affects human health. Vitamin D deficiency is a global health problem, affecting approximately 60% of adults worldwide, and has been implicated in a range of different types of diseases, e.g., cancer. Vitamin D is involved in the regulation of cell proliferation, differentiation, energetic metabolism, and different types of cell death (e.g., apoptosis, autophagy, etc.). In physiological conditions, it is also able to modulate immune responses, angiogenesis, etc., which belongs to fundamental cancer-related processes. Vitamin D deficiency has been associated with an increased risk of some types of cancer, e.g., colorectal, breast, ovarian, prostate, pancreatic, etc. The role of vitamin D in cancer prevention, carcinogenesis, and cancer treatment is still under investigation and depends on the type of cancer. This review summarizes the role of vitamin D in all three above-mentioned aspects and discusses the mechanism of action and potential possibilities in cancer treatment.
 Download the PDF from VitaminDWiki

---

References

1. JAROSLAWSKA J, CARLBERG C. In Vivo Regulation of Sig­nal Transduction Pathways by Vitamin D Stabilizes Homeo­stasis of Human Immune Cells and Counteracts Molecular Stress. Int J Mol Sci 2023; 24: 14632. https://doi.org/10.3390/ ijms241914632
2. JAROSLAWSKA J, GHOSH DASTIDAR R, CARLBERG C. In vivo vitamin D target genes interconnect key signaling pathways of innate immunity. PLoS One 2024; 19: e0306426. https://doi.org/10.1371/journal.pone.0306426
3. BOUILLON R, VAN CROMPHAUT S, CARMELIET G. In­testinal calcium absorption: Molecular vitamin D mediated mechanisms. J Cell Biochem 2003; 88: 332-339. https://doi. org/10.1002/jcb.10360
4. MARKIEWICZ A, BROZYNA AA, PODGORSKA E, ELAS M, URBANSKA K et al. Vitamin D receptors (VDR), hy­droxylases CYP27B1 and CYP24A1 and retinoid-related or­phan receptors (ROR) level in human uveal tract and ocular melanoma with different melanization levels. Sci Rep 2019; 9: 9142. https://doi.org/10.1038/s41598-019-45161-8
5. HUO X, SUN H, QIAN Q, MA X, PENG P et al. CYP27B1 Downregulation: A New Molecular Mechanism Regulating EZH2 in Ovarian Cancer Tumorigenicity. Front Cell Dev Biol 2020; 8: 561804. https://doi.org/10.3389/fcell.2020.561804
6. VIDIGAL VM, SILVA TD, DE OLIVEIRA J, PIMENTA CAM, FELIPE AV et al. Genetic polymorphisms of vitamin D receptor (VDR), CYP27B1 and CYP24A1 genes and the risk of colorectal cancer. Int J Biol Markers. 2017; 32: e224- e230. https://doi.org/10.5301/jbm.5000248
7. VOUTSADAKIS IA. Vitamin D receptor (VDR) and metab­olizing enzymes CYP27B1 and CYP24A1 in breast cancer. Mol Biol Rep 2020; 47: 9821-9830. https://doi.org/10.1007/ s11033-020-05780-1
8. NORMAN AW Minireview: vitamin D receptor: new as­signments for an already busy receptor. Endocrinology 2006; 147: 5542-5548. https://doi.org/10.1210/en.2006-0946
9. ZHAO M, LIU Z, SHI H, SONG J. Prognostic role of vita­min D receptor in digestive system tumours: A systematic review and preliminary meta-analysis. PLoS One 2023; 18: e0289598. https://doi.org/10.1371/journal.pone.0289598
10. WILLIAMS JD, AGGARWAL A, SWAMI S, KRISHNAN AV, JI L et al. Tumor Autonomous Effects of Vitamin D Deficien­cy Promote Breast Cancer Metastasis. Endocrinology 2016; 157: 1341-1347. https://doi.org/10.1210/en.2015-2036
11. TEICHERT AE, ELALIEH H, ELIAS PM, WELSH J, BIKLE DD. Overexpression of Hedgehog Signaling Is Associated with Epidermal Tumor Formation in Vitamin D Receptor- Null Mice. J Invest Dermatol 2011; 131: 2289-2297. https:// doi.org/10.1038/jid.2011.196
12. JIANG YJ, TEICHERT AE, FONG F, ODA Y, BIKLE DD. 1a,25(OH)2-Dihydroxyvitamin D3/VDR protects the skin from UVB-induced tumor formation by interacting with the ß-catenin pathway. J Steroid Biochem Mol Biol 2013; 136: 229-232. https://doi.org/10.1016/j.jsbmb.2012.09.024
13. THABET RH, GOMAA AA, MATALQAH LM, SHALABY EM. Vitamin D: an essential adjuvant therapeutic agent in breast cancer. J Int Med Res 2022; 50: 3000605221113800. https://doi.org/10.1177/03000605221113800
14. OBARA W, SUZUKI Y, KATO K, TANJI S, KONDA R et al. Vitamin D receptor gene polymorphisms are associated with increased risk and progression of renal cell carcinoma in a Japanese population. Int J Urol 2007; 14: 483-487. https:// doi.org/10.1111/j.1442-2042.2007.01771.x
15. ANIC GM, THOMPSON RC, NABORS LB, OLSON JJ, BROWNING JE et al. An exploratory analysis of com­mon genetic variants in the vitamin D pathway including genome-wide associated variants in relation to glioma risk and outcome. Cancer Causes Control 2012; 23: 1443-1449. https://doi.org/10.1007/s10552-012-0018-7
16. HUSS L, GULZ-HAAKE I, NILSSON E, TRYGGVADOT- TIR H, NILSSON L et al. The Vitamin D Receptor as a Prog­nostic Marker in Breast Cancer-A Cohort Study. Nutrients 2024; 16: 931. https://doi.org/10.3390/nu16070931
17. KHALID AT, MOORE CG, HALL C, OLABOPO F, RO- ZARIO NL et al. Utility of sun-reactive skin typing and mel­anin index for discerning vitamin D deficiency. Pediatr Res 2017; 82: 444-451. https://doi.org/10.1038/pr.2017.114
18. DESANTIS CE, SIEGEL RL, SAUER AG, MILLER KD, FEDEWA SA et al. Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial dis­parities. CA Cancer J Clin 2016; 66: 290-308. https://doi. org/10.3322/caac.21340
19. MONTEITH GR, PREVARSKAYA N, ROBERTS-THOM­SON SJ. The calcium-cancer signalling nexus. Nat Rev Can­cer 2017; 17: 373-380. https://doi.org/10.1038/nrc.2017.1
20. BERNICHTEIN S, PIGAT N, BARRY DELONGCHAMPS N, BOUTILLON F, VERKARRE V et al. Vitamin D3 Pre­vents Calcium-Induced Progression of Early-Stage Prostate Tumors by Counteracting TRPC6 and Calcium Sensing Re­ceptor Upregulation. Cancer Res 2017; 77: 355-365. https:// doi.org/10.1158/0008-5472.Can-16-0687
21. TORFADOTTIR JE, UUSI-RASI K. Calcium - a scoping review for Nordic Nutrition Recommendations 2023. Food Nutr Res 2023; 67. https://doi.org/10.29219/fnr.v67.10303
22. LIU N, LI X, FU Y, LI Y, LU W et al. Inhibition of lung cancer by vitamin D depends on downregulation of histidine-rich calcium-binding protein. J Adv Res 2021; 29: 13-22. https:// doi.org/10.1016/j.jare.2020.08.013
23. NOWAK JI, OLSZEWSKA AM, WIERZBICKA JM, GE­BERT M, BARTOSZEWSKI R et al. VDR and PDIA3 Are Essential for Activation of Calcium Signaling and Mem­brane Response to 1,25(OH)2D3 in Squamous Cell Car­cinoma Cells. Cells 2024; 13: 11. https://doi.org/10.3390/ cells13010011
24. YIN T, ZHU X, HE Z, BAI H, SHEN C et al. The causal re­lationship between 25-hydroxyvitamin D and serum lipids levels: A bidirectional two-sample mendelian randomization 37 study. PLoS One 2024; 19: e0287125. https://doi.org/10.1371/ journal.pone.0287125
25. ZHANG B, DONG X. The unique association between se­rum 25-hydroxyvitamin D concentrations and blood lipid profiles in agriculture, forestry, and fishing occupations:Insights from NHANES 2001-2014. PLoS One 2024; 19: e0297873. https://doi.org/10.1371/journal.pone.0297873
26. MOK EHK, LEE TKW. The Pivotal Role of the Dysregula­tion of Cholesterol Homeostasis in Cancer: Implications for Therapeutic Targets. Cancers (Basel) 2020; 12. https://doi. org/10.3390/cancers12061410
27. GONZALEZ-ORTIZ A, GALINDO-HERNANDEZ O, HERNANDEZ-ACEVEDO GN, HURTADO-URETA g, GARCiA-GONZALEZ V. Impact of cholesterol-pathways on breast cancer development, a metabolic landscape. J Cancer 2021; 12: 4307-4321. https://doi.org/10.7150/jca.54637
28. RODRIGUES DOS SANTOS C, FONSECA I, DIAS S, MENDES DE ALMEIDA JC. Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression. BMC Cancer 2014; 14: 132. https://doi.org/10.1186/1471- 2407-14-132
29. SEGALA G, DE MEDINA P, IULIANO L, ZERBINATI C, PAILLASSE MR et al. 5,6-Epoxy-cholesterols contribute to the anticancer pharmacology of tamoxifen in breast cancer cells. Biochem Pharmacol 2013; 86: 175-189. https://doi. org/10.1016/j.bcp.2013.02.031
30. FARWELL WR, SCRANTON RE, LAWLER EV, LEW RA, BROPHY MT et al. The Association Between Statins and Cancer Incidence in a Veterans Population. J Natl Can­cer Inst 2008; 100: 134-139. https://doi.org/10.1093/jnci/ djm286
31. CALLE EE, RODRIGUEZ C, WALKER-THURMOND K, THUN MJ. Overweight, obesity, and mortality from can­cer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003; 348: 1625-1638. https://doi.org/10.1056/NEJ- Moa021423
32. SHANMUGALINGAM T, CRAWLEY D, BOSCO C, MELVIN J, ROHRMANN S et al. Obesity and cancer: the role of vitamin D. BMC Cancer 2014; 14: 712. https://doi. org/10.1186/1471-2407-14-712
33. NOWAK MM, NIEMCZYK M, GOtÇBIEWSKI S, P4.CZEK L. Impact of Body Mass Index on All-Cause Mortality in Adults: A Systematic Review and Meta-Analysis. J Clin Med 2024; 13: 2305. https://doi.org/10.3390/jcm13082305
34. WOLIN KY, CARSON K, COLDITZ GA. Obesity and can­cer. Oncologist 2010; 15: 556-565. https://doi.org/10.1634/ theoncologist.2009-0285
35. MA Y, YANG Y, WANG F, ZHANG P, SHI C et al. Obesity and risk of colorectal cancer: a systematic review of pro­spective studies. PLoS One 2013; 8: e53916. https://doi. org/10.1371/journal.pone.0053916
36. ARNOLD M, JIANG L, STEFANICK ML, JOHNSON KC, LANE DS et al. Duration of Adulthood Overweight, Obesity, and Cancer Risk in the Women’s Health Initiative: A Longi­tudinal Study from the United States. PLoS Med 2016; 13: e1002081. https://doi.org/10.1371/journal.pmed.1002081
37. RECALDE M, PISTILLO A, DAVILA-BATISTA V, LEITZMANN M, ROMIEU I et al. Longitudinal body mass index and cancer risk: a cohort study of 2.6 million Catalan adults. Nat Commun 2023; 14: 3816. https://doi.org/10.1038/ s41467-023-39282-y
38. PEREIRA-SANTOS M, COSTA PRF, ASSIS AMO, SANTOS CAST, SANTOS DB. Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obesity Rev 2015; 16: 341-349. https://doi.org/10.1111/obr.12239
39. GANDINI S, BONIOL M, HAUKKA J, BYRNES G, COX B 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. https://doi.org/10.1002/ijc.25439
40. ALMAGHRBI H, AL-SHAFAI M, AL-ASMAKH M, BAWA- DI H. Association of Vitamin D Genetic Risk Score with Noncommunicable Diseases: A Systematic Review. Nutri­ents 2023; 15. https://doi.org/10.3390/nu15184040
41. SOARES MJ, CHAN SHE PING-DELFOS W, GHANBARI MH. Calcium and vitamin D for obesity: a review of ran­domized controlled trials. Eur J Clin Nutr 2011; 65: 994­1004. https://doi.org/10.1038/ejcn.2011.106
42. ZHU W, CAI D, WANG Y, LIN N, HU Q et al. Calcium plus vitamin D3 supplementation facilitated Fat loss in over­weight and obese college students with very-low calcium consumption: a randomized controlled trial. Nutr J 2013; 12: 8. https://doi.org/10.1186/1475-2891-12-8
43. ZEMEL MB. Mechanisms of Dairy Modulation of Adipos­ity. J Nutr 2003; 133: 252S-256S. https://doi.org/10.1093/ jn/133.1.252S
44. SUBIH HS, ZUETER Z, OBEIDAT BM, AL-QUDAH MA, JANAKAT SA et al. A high weekly dose of cholecalciferol and calcium supplement enhances weight loss and improves health biomarkers in obese women. Nutr Res 2018; 59: 53­64. https://doi.org/10.1016/j.nutres.2018.07.01
45. LEE JW, GU HO, JUNG Y, JUNG Y, SEO SY et al. Candesar- tan, an angiotensin-II receptor blocker, ameliorates insulin resistance and hepatosteatosis by reducing intracellular cal­cium overload and lipid accumulation. Exp Mol Med 2023; 55: 910-925. https://doi.org/10.1038/s12276-023-00982-6
46. CUI M, ZHAO Y, ZHANG Z, ZHAO Y, HAN S et al. IL-8, MSPa, MIF, FGF-9, ANG-2 and AgRP collection were iden­tified for the diagnosis of colorectal cancer based on the sup­port vector machine model. Cell Cycle 2021; 20: 781-791. https://doi.org/10.1080/15384101.2021.1903208
47. ZOLOT J. Vitamin D, Omega-3 Fatty Acids Don’t Lower Rates of Cancer or CVD. Am J Nurs 2019; 119: 15. https:// doi.org/10.1097/01.NAJ.0000553195.75599.75
48. ALTUNDAG K. Combined use of vitamin D and omega-3 fatty acid in breast cancer patients might be more beneficial for reducing aromatase inhibitors-associated arthralgia. J BUON 2019; 24: 862.
49. ABUGOUKH TM, AL SHARABY A, ELSHAIKH AO, JODA M, MADNI A et al. Does Vitamin D Have a Role in Diabetes? Cureus 2022; 14: e30432. https://doi.org/10.7759/ cureus.30432
50. DAVIES MJ, ARODA VR, COLLINS BS, GABBAY RA, GREEN J et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Dia­betes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022; 45: 2753­2786. https://doi.org/10.2337/dci22-0034
51. PLUDOWSKI P, TAKACS I, BOYANOV M, BELAYA Z, DI- ACONU CC et al. Clinical Practice in the Prevention, Diag­nosis and Treatment of Vitamin D Deficiency: A Central and Eastern European Expert Consensus Statement. Nutrients 2022; 14. https://doi.org/10.3390/nu14071483
52. GARLAND FC, GARLAND CF, GORHAM ED, YOUNG JF. Geographic variation in breast cancer mortality in the Unit­ed States: a hypothesis involving exposure to solar radiation. Prev Med 1990; 19: 614-622. https://doi.org/10.1016/0091- 7435(90)90058-r
53. INGRAHAM BA, BRAGDON B, NOHE A. Molecu­lar basis of the potential of vitamin D to prevent can­cer. Curr Med Res Opin 2008; 24: 139-149. https://doi. org/10.1185/030079908x253519
54. KHAMIS A, SALZER L, SCHIEGNITZ E, STAUBER RH, GÜL D. The Magic Triangle in Oral Potentially Malignant Disorders: Vitamin D, Vitamin D Receptor, and Malignan­cy. Int J Mol Sci 2023; 24: 15058. https://doi.org/10.3390/ ijms242015058
55. WEINSTEIN SJ, MONDUL AM, LAYNE TM, YU K, HUANG J et al. Prediagnostic Serum Vitamin D, Vitamin D Binding Protein Isoforms, and Cancer Survival. JNCI Can­cer Spectr 2022; 6: pkac019. https://doi.org/10.1093/jncics/ pkac019
56. ZHANG R, ZHANG Y, LIU Z, PEI Y, XU P et al. Association between Vitamin D Supplementation and Cancer Mortality: A Systematic Review and Meta-Analysis. Cancers 2022; 14: 3717. https://doi.org/10.3390/cancers14153717
57. BARRY EL, PEACOCK JL, REES JR, BOSTICK RM, ROB­ERTSON DJ et al. Vitamin D Receptor Genotype, Vitamin D₃ Supplementation, and Risk of Colorec­tal Adenomas. JAMA Oncol 2017; 3: 628. https://doi. org/10.1001/jamaoncol.2016.5917
58. CHATTERJEE I, ZHANG Y, ZHANG J, LU R, XIA Y et al. Overexpression of Vitamin D Receptor in Intestinal Epithe- lia Protects Against Colitis via Upregulating Tight Junction Protein Claudin 15. J Crohns Colitis 2021; 15: 1720-1736. https://doi.org/10.1093/ecco-jcc/jjab044
59. CHANDLER PD, CHEN WY, AJALA ON, HAZRA A, COOK N et al. Effect of Vitamin D₃ Supple­ments on Development of Advanced Cancer. JAMA Netw Open 2020; 3: e2025850. https://doi.org/10.1001/jamanet- workopen.2020.25850
60. FELDMAN D, KRISHNAN AV, SWAMI S, GIOVANNUCCI E, FELDMAN BJ. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer 2014; 14: 342-357. https://doi.org/10.1038/nrc3691
61. AVILA E, NORIEGA-MEJÍA BJ, GONZÁLEZ-MACÍAS J, CORTES-HERNÁNDEZ U, GARCÍA-QUIROZ J et al. The Preventive Role of the Vitamin D Endocrine System in Cervical Cancer. Int J Mol Sci 2023; 24: 8665. https://doi. org/10.3390/ijms24108665
    - - - - - start of references in table - - - - - - - - -
62. TORRES A, CAMESELLE C, OTERO P, SIMAL-GANDA­RA J. The Impact of Vitamin D and Its Dietary Supplemen­tation in Breast Cancer Prevention: An Integrative Review. Nutrients 2024; 16: 573. https://doi.org/10.3390/nu16050573
63. GUYONNET E, KIM SJ, PULLELLA K, ZHANG CXW, MC- CUAIG JM et al. Vitamin D and Calcium Supplement Use and High-Risk Breast Cancer: A Case-Control Study among BRCA1 and BRCA2 Mutation Carriers. Cancers 2023; 15: 2790. https://doi.org/10.3390/cancers15102790
64. VALLÈS X, ALONSO MH, LÓPEZ-CALEYA JF, DÍEZ-OB- RERO V, DIERSSEN-SOTOS T et al. Colorectal cancer, sun exposure and dietary vitamin D and calcium intake in the MCC-Spain study. Environ Int 2018; 121: 428-434. https:// doi.org/10.1016/j.envint.2018.09.030
65. LI J, QIN S, ZHANG S, LU Y, SHEN Q et al. Serum vita­min D concentration, vitamin D-related polymorphisms, and colorectal cancer risk. Int J Cancer 2023; 153: 278-289. https://doi.org/10.1002/ijc.34521
66. MAALMI H, WALTER V, JANSEN L, BOAKYE D, SCHÖTTKER B et al. Association between Blood 25-Hy- droxyvitamin D Levels and Survival in Colorectal Cancer Patients: An Updated Systematic Review and Meta-Analysis. Nutrients 2018; 10: 896. https://doi.org/10.3390/nu10070896
67. GWENZI T, SCHROTZ-KING P, SCHÖTTKER B, HOFF­MEISTER M, BRENNER H. Vitamin D Status, Cdx2 Genotype, and Colorectal Cancer Survival: Population- Based Patient Cohort. Nutrients 2023; 15: 2717. https://doi. org/10.3390/nu15122717
68. STROOMBERG HV, VOJDEMAN FJ, MADSEN CM, HEL- GSTRAND JT, SCHWARZ P et al. Vitamin D levels and the risk of prostate cancer and prostate cancer mortality. Acta Oncol 2021; 60: 316-322. https://doi.org/10.1080/028418 6X.2020.1837391
69. PENG SM, YU N, CHE J, XU JY, CHEN GC et al. Total, bioavailable and free 25-hydroxyvitamin D are associated with the prognosis of patients with non-small cell lung can­cer. Cancer Causes Control 2022; 33: 983-993. https://doi. org/10.1007/s10552-022-01579-6
70. ZIGMONT V, GARRETT A, PENG J, SEWERYN M, REM- PALA GA et al. Association Between Prediagnostic Serum 25-Hydroxyvitamin D Concentration and Glioma. Nutr Cancer 2015; 67: 1120-1130. https://doi.org/10.1080/01635 581.2015.1073757
71. SONG Y, LU H, CHENG Y. To identify the association be­tween dietary vitamin D intake and serum levels and risk or prognostic factors for melanoma-systematic review and meta-analysis. BMJ Open 2022; 12: e052442. https://doi. org/10.1136/bmjopen-2021-052442
72. ZHOU C, ZHANG Y, YE Z, HE P, ZHANG Y et al. Relation­ship among serum 25-hydroxyvitamin D, fibrosis stage, ge­netic susceptibility, and risk of severe liver disease. Nutrition 2024; 119: 112320. https://doi.org/10.1016/j.nut.2023.112320
73. SHEN Y, XIA J, YI C, LI T, WANG P et al. The association between circulating 25-hydroxyvitamin D and pancreatic cancer: a systematic review and meta-analysis of obser­vational studies. Eur J Nutr 2024; 63: 653-672. https://doi. org/10.1007/s00394-023-03302-w
74. BERSANELLI M, CORTELLINI A, LEONETTI A, PARISI A, TISEO M et al. Systematic vitamin D supplementation is associated with improved outcomes and reduced thyroid adverse events in patients with cancer treated with immune checkpoint inhibitors: results from the prospective PROVI­DENCE study. Cancer Immunol Immunother 2023; 72: 3707-3716. https://doi.org/10.1007/s00262-023-03522-3
75. WILSON WESTMARK NL, SROUSSI H, TAMAYO I, VILLA A. Vitamin D status in patients with oropharyngeal cancer: Association with HPV status and prognosis. Oral Dis 2023; 29: 542-546. https://doi.org/10.1111/odi.13965
76. ABDELGAWAD A, HASHEM A, MOSBAH A, EISSA LA. A prospective trial investigating the role of Serum 25-Hy- droxyvitamin D in diagnosis and prognosis of bladder can­cer. PLoS One 2022; 17: e0266371. https://doi.org/10.1371/ journal.pone.0266371
77. ABDULRAZAQ ZA, AL-OUQAILI MTS, TALIB NM. The impact of circulating 25-hydroxyvitamin D and vitamin D receptor variation on leukemia-lymphoma outcome: Molec­ular and cytogenetic study. Saudi J Biol Sci 2024; 31: 103882. https://doi.org/10.1016/j.sjbs.2023.103882
    - - - - - - - - - - - - - -
78. CARLBERG C, MUNOZ A. An update on vitamin D sig­naling and cancer. Semin Cancer Biol 2022; 79: 217-230. https://doi.org/10.1016/j.semcancer.2020.05.018
79. HANAHAN D, WEINBERG RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674. https://doi. org/10.1016/j.cell.2011.02.013
80. LIU Y, MENG X, ZHANG X, HE L, WANG Y. Vitamin D Inhibits Colorectal Cancer Cell Proliferation, Migration and Invasion via Downregulating the Notch1 Pathway. Cell Mol Biol (Noisy-le-grand) 2023; 69: 164-167. https://doi. org/10.14715/cmb/2023.69.7.26
81. GARCIA-MARTINEZ JM, CHOCARRO-CALVO A, MAR- TINEZ-USEROS J, FERNANDEZ-ACENERO MJ, FIUZA MC et al. Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer. Elife 2023; 12: RP86913. https://doi.org/10.7554/eLife.86913
82. ZHANG Y, WANG X. Targeting the Wnt/beta-catenin sig­naling pathway in cancer. J Hematol Oncol 2020; 13: 165. https://doi.org/10.1186/s13045-020-00990-3
83. LING Y, XU F, XIA X, DAI D, SUN R et al. Vitamin D re­ceptor regulates proliferation and differentiation of thyroid carcinoma via the E-cadherin-beta-catenin complex. J Mol Endocrinol 2022; 68: 137-151. https://doi.org/10.1530/JME- 21-0167
84. POURSOLTANI F, NEJATI V, PAZHANG Y, REZAIE J. Su- lindac and vitamin D3 synergically inhibit proliferation of MCF-7 breast cancer cell through AMPK/Akt/beta-catenin axis in vitro. Cell Biochem Funct 2021; 39: 991-997. https:// doi.org/10.1002/cbf.3668
85. YU J, SUN Q, HUI Y, XU J, SHI P et al. Vitamin D receptor prevents tumour development by regulating the Wnt/beta- catenin signalling pathway in human colorectal cancer. BMC Cancer 2023; 23: 336. https://doi.org/10.1186/s12885-023- 10690-z
86. ZHANG Y, LI Y, WEI Y, CONG L. Molecular Mechanism of Vitamin D Receptor Modulating Wnt/beta-catenin Signaling Pathway in Gastric Cancer. J Cancer 2023; 14: 3285-3294. https://doi.org/10.7150/jca.81034
87. HUANG CY, WENG YT, LI PC, HSIEH NT, LI CI et al. Calcitriol Suppresses Warburg Effect and Cell Growth in Human Colorectal Cancer Cells. Life (Basel) 2021; 11: 963. https://doi.org/10.3390/life11090963
88. SONGYANG Y, SONG T, SHI Z, LI W, YANG S et al. Effect of vitamin D on malignant behavior of non-small cell lung can­cer cells. Gene 2021; 768: 145309. https://doi.org/10.1016Zj. gene.2020.145309
89. GLAVIANO A, FOO ASC, LAM HY, YAP KCH, JACOT W et al. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Mol Cancer 2023; 22: 138. https://doi.org/10.1186/s12943-023-01827-6
90. ALMAIMANI RA, ASLAM A, AHMAD J, EL-READI MZ, EL-BOSHY ME et al. In Vivo and In Vitro Enhanced Tumor- icidal Effects of Metformin, Active Vitamin D(3), and 5-Flu- orouracil Triple Therapy against Colon Cancer by Modulat­ing the PI3K/Akt/PTEN/mTOR Network. Cancers (Basel) 2022; 14: 1538. https://doi.org/10.3390/cancers14061538
91. IDRIS S, REFAAT B, ALMAIMANI RA, AHMED HG, AH­MAD J et al. Enhanced in vitro tumoricidal effects of 5-Flu- orouracil, thymoquinone, and active vitamin D(3) triple therapy against colon cancer cells by attenuating the PI3K/ AKT/mTOR pathway. Life Sci 2022; 296: 120442. https://doi. org/10.1016/j.lfs.2022.120442
92. VEERESH PKM, BASAVARAJU CG, DALLAVALASA S, ANANTHARAJU PG, NATRAJ SM et al. Vitamin D3 In­hibits the Viability of Breast Cancer Cells In Vitro and Eh­rlich Ascites Carcinomas in Mice by Promoting Apoptosis and Cell Cycle Arrest and by Impeding Tumor Angiogenesis. Cancers (Basel) 2023; 15: 4833. https://doi.org/10.3390/can- cers15194833
93. ALATAWI FS, FARIDI U. Anticancer and anti-metastasis activity of 1,25 dihydroxycholecalciferols and genistein in MCF-7 and MDA-MB-231 breast cancer cell lines. Heli- yon 2023; 9: e21975. https://doi.org/10.1016Aj.heliyon.2023. e21975
94. KIM JH, PARK WH, SUH DH, KIM K, NO JH et al. Cal­citriol Combined With Platinum-based Chemotherapy Suppresses Growth and Expression of Vascular Endothelial Growth Factor of SKOV-3 Ovarian Cancer Cells. Antican­cer Res 2021; 41: 2945-2952. https://doi.org/10.21873/anti- canres.15076
95. KHAMIS A, GUL D, WANDREY M, LU Q, KNAUER SK et al. The Vitamin D Receptor-BIM Axis Overcomes Cisplatin Resistance in Head and Neck Cancer. Cancers (Basel) 2022; 14: 5131. https://doi.org/10.3390/cancers14205131
96. VAUPEL P, MULTHOFF G. Revisiting the Warburg effect: historical dogma versus current understanding. J Physiol 2021; 599: 1745-1757. https://doi.org/10.1113/JP278810
97. JIE L, HENGYUE W, TING H. Calcitriol suppresses gastric cancer progression and cisplatin resistance by inhibiting glycolysis and M2 macrophage polarization through inhibi­tion of mTOR activation. Environ Toxicol 2024; 39: 830-839. https://doi.org/10.1002/tox.23975
98. YUN CW, LEE SH. The Roles of Autophagy in Can­cer. Int J Mol Sci 2018; 19: 3466. https://doi.org/10.3390/ ijms19113466
99. LI Y, COOK KL, YU W, JIN L, BOUKER KB et al. Inhibi­tion of Antiestrogen-Promoted Pro-Survival Autophagy and Tamoxifen Resistance in Breast Cancer through Vitamin D Receptor. Nutrients 2021; 13: 1715. https://doi.org/10.3390/ nu13051715
100. TAVERA-MENDOZA LE, WESTERLING T, LIBBY E, MARUSYK A, CATO L et al. Vitamin D receptor regulates autophagy in the normal mammary gland and in luminal breast cancer cells. Proc Natl Acad Sci U S A 2017; 114: E2186-E2194. https://doi.org/10.1073/pnas.1615015114
101. TUTTIS K, MACHADO ART, SANTOS P, ANTUNES LMG. Sulforaphane Combined with Vitamin D Induces Cy­totoxicity Mediated by Oxidative Stress, DNA Damage, Au­tophagy, and JNK/MAPK Pathway Modulation in Human Prostate Tumor Cells. Nutrients 2023; 15: 2742. https://doi. org/10.3390/nu15122742
102. SETIAWAN I, LESMANA R, GOENAWAN H, SUARDI D, GATERA VA et al. Calcitriol potentially alters HeLa cell vi­ability via inhibition of autophagy. J Cancer Res Ther 2022; 18: 1144-1151. https://doi.org/10.4103/jcrt.JCRT_82_20
103. MOLASSIOTIS A, CHENG HL, LEUNG KT, LI YC, WONG KH et al. Risk factors for chemotherapy-induced periph­eral neuropathy in patients receiving taxane- and platinum- based chemotherapy. Brain Behav 2019; 9: e01312. https:// doi.org/10.1002/brb3.1312
104. JENNARO TS, FANG F, KIDWELL KM, SMITH EML, VAN- GIPURAM K et al. Vitamin D deficiency increases severity of paclitaxel-induced peripheral neuropathy. Breast Can­cer Res Treat 2020; 180: 707-714. https://doi.org/10.1007/ s10549-020-05584-8
105. CHEN CS, ZIRPOLI G, BARLOW WE, BUDD GT, MCK- IVER B et al. Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221. J Natl Compr Canc Netw 2023; 21: 1172-1180.e1173. https:// doi.org/10.6004/jnccn.2023.7062
106. WEI D, WANG L, ZUO X, BRESALIER RS. Vitamin D: Promises on the Horizon and Challenges Ahead for Fighting Pancreatic Cancer. Cancers (Basel) 2021; 13: 2716. https:// doi.org/10.3390/cancers13112716

---

VitaminDWiki – Cancer category contains:

• Cancer 295 items Overview Cancer and vitamin D
• Cancer and Vitamin D - many studies
• After Cancer Diagnosis 113 items
• Bladder Cancer 28 items
• Breast Cancer 259 items Overview Breast Cancer and Vitamin D
• Colon Cancer 145 items Overview Cancer-Colon and vitamin D
• Leukemia 19 items
• Liver Cancer 17 items
• Lung Cancer 55 items Overview Lung cancer and vitamin D
• Lymphoma Cancer 26 items
• Other Cancer 66 items
• Ovarian Cancer 26 items
• Pancreatic Cancer 58 items
• Prostate Cancer 103 items Overview Prostate Cancer and Vitamin D
• Skin Cancer 121 items Overview Suntan, melanoma and vitamin D
• Childhood Cancers - Vitamin D can help - many studies
• Easiest way to treat cancer – take Vitamin D – Nov 2022
• 13 Cancers are helped by Vitamin D – Biobank July 2023
• 2X increase of 14 cancers in non-seniors in 20 years (low vitamin D) – Sept 2022
• Vitamin D prevents and treats cancer in many ways – May 2021
• Those with recent cancer diagnosis had 7X increased risk of COVID-19 (more if A-A )- Dec 2020
• Deaths from many types of Cancer associated with low vitamin D- review of meta-analyses Sept 2020
• Cancer incidence and mortality is decreased if 40-60 ng of Vitamin D – April 2019
• 8 ways that Cancer might be prevented by Vitamin D - June 2019
• Cancer stem cells and Vitamin D - many studies
• Vitamin D Reduces Cancer Risk - Why Scientists Accept It but Physicians Do Not - Feb 2019
• Overview of Vitamin D Actions in Cancer – 31 page chapter in a book – 2018
• Vitamin D prevents breast cancer, reduces BC mortality, and reduces BC chemotherapy problems – Sept 2018
• Diagnosed with breast cancer – take vitamin D to cut chance of death by half – July 2018
• Melanoma 25 X more likely if low vitamin D – Feb 2018
• Better Cancer survival if higher vitamin D a decade earlier (esp. Melanoma, Kidney, Prostate)– Aug 2018

Cancers get less Vitamin D when there is a poor Vitamin D Receptor

• Vitamin D Receptor pages in VitaminDWiki with CANCER in title 86 as of July 2023
• Cancer and the Vitamin D Receptor, a primer – Sept 2017
• Vitamin D Receptor (Cancers OR Viruses) - many studies
• Risk of Cancer increased if poor Vitamin D Receptor – meta-analysis of 73 studies Jan 2016
• Cancer (general) and VDR 23 articles
• Breast Cancer and VDR 24 articles
• Colon Cancer and VDR 13 articles
• Prostate Cancer and VDR 7 articles
• Skin Cancer and VDR 10 articles
  • Note some Health problems, such as some Cancers, protect themselves
    by actively reducing Receptor activation

---

Note: Treating cancers need >2X higher Vitamin D levels than for prevention
suspect that cancers protect themselves by changing Vitamin D genes

---

35+ Genetics pages have CANCER in the title

The list is automatically updated

---

89+ VDR pages have CANCER in the title

The list is automatically updated

---

55+ pages have both CANCER AND PREVENT in the title (a subset of all relevant studies)

The list is automatically updated

---

40-150 ng of Vitamin D needed to treat health problems - (less D needed to prevent)

Vitamin D	Treats
150 ng	Multiple Sclerosis *
80 ng	Cluster Headache * Reduced office visits by 4X *
70 ng	Sleep *
60 ng	Breast Cancer death reduced 60% Preeclampsia RCT
50 ng	COVID-19 T1 Diabetes Fertility Psoriasis Infections Review Infection after surgery
40 ng	Breast Cancer 65% lower risk Depression ACL recovery Hypertension Asthma?
30 ng	Rickets

* Evolution of experiments with patients, often also need co-factors