Vitamin D

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This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.

Improving bone mineral density behaviors

Men with prostate cancer receiving androgen deprivation therapy showed higher rate of bone mineral density testing when receiving both a patient bone health pamphlet and support from a bone health care coordinator compared to usual care. Men receiving a patient bone health pamphlet and brief recommendations for their family physician showed more use of calcium and vitamin D and orders of bone mineral density tests in a mid-sized RCT.¹Alibhai SMH, Breunis H et al. Improving bone health in men with prostate cancer receiving androgen deprivation therapy: results of a randomized phase 2 trial. Cancer. 2018 Mar sa15;124(6):1132-1140. 

Vitamin D receptor and gene polymorphisms

Genetic variants may influence the response of the vitamin D receptor (VDR) to vitamin D treatment.

Vitamin D effects as a whole

• Allelic variants were related to a higher transcription of VDR gene and a higher activity of VDR receptor.²Amadori D, Serra P et al. Vitamin D receptor polymorphisms or serum levels as key drivers of breast cancer development? The question of the vitamin D pathway. Oncotarget. 2017 Feb 21;8(8):13142-13156.
• A link has been shown among gene polymorphisms FokI, BsmI, TaqI, and ApaI and tumorigenesis.³Rai V, Abdo J, Agrawal S, Agrawal DK. Vitamin D receptor polymorphism and cancer: an update. Anticancer Research. 2017 Aug;37(8):3991-4003.

Cancer survival

• The protein expression level of VDR in entire breast cancer cells evaluated by immunohistochemistry is related to the overall survival of breast cancer patients.⁴Xu H, Liu Z, Shi H, Wang C. Prognostic role of vitamin D receptor in breast cancer: a systematic review and meta-analysis. BMC Cancer. 2020 Nov 1;20(1):1051. 
• Better survival among people with advanced non–small-cell lung cancer with the C/C genotype of the FokI polymorphism compared to C/T or T/T genotypes, although 25(OH)D levels had no main effect on survival, in a mid-sized observational study⁵Heist RS, Zhou W et al. Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer. Journal of Clinical Oncology. 2008 Dec 1;26(34):5596-602.

Risk of recurrence

• Single nucleotide polymorphisms (SNPs) in retinoid-X receptor alpha (RXRA) may be a predictor for disease-free survival with breast cancer.⁶Pande M, Thompson PA et al. Genetic variants in the vitamin D pathway and breast cancer disease-free survival. Carcinogenesis. 2013 Mar;34(3):587-94.

Risk of cancer

Cancer as a whole

• Some differences were found, partially explained by minor allele frequency (MAF), for colorectal cancer, ovarian and prostate cancer in Caucasian and prostate cancer in Asian populations.⁷Gnagnarella P, Raimondi S et al. Ethnicity as modifier of risk for Vitamin D receptors polymorphisms: comprehensive meta-analysis of all cancer sites. Critical Reviews in Oncology/Hematology. 2021 Feb;158:103202.
• The rs12785878, rs1790349, and rs12794714 SNPs related to vitamin D-metabolizing enzymes might potentially be biomarkers for cancer susceptibility.⁸Wen J, Li J, Liang X, Wang A. Association of polymorphisms in vitamin D-metabolizing enzymes DHCR7 and CYP2R1 with cancer susceptibility: a systematic review and meta-analysis. Disease Markers. 2021 May 22;2021:6615001.
• There is a correlation between the TaqI polymorphism of vitamin D receptor (VDR)  and the risk of tobacco-related cancers.⁹Laczmanski L, Laczmanska I, Lwow F. Association of select vitamin D receptor gene polymorphisms with the risk of tobacco-related cancers—a meta-analysis. Scientific Reports. 2019 Nov 5;9(1):16026.
• The rs4588 and rs7041 polymorphisms, related to vitamin D metabolism, were significantly associated with overall cancer risk. Stratification analyses of ethnicity indicated that rs4588 polymorphism significantly increased cancer risk in Caucasians and Asians, while rs7041 polymorphism significantly increased cancer risk in Asians.¹⁰Zhu M, Tan Z et al. Association of the vitamin D metabolism gene GC and CYP27B1 polymorphisms with cancer susceptibility: a meta-analysis and trial sequential analysis. Bioscience Reports. 2019 Sep 13;39(9):BSR20190368.
• The rs2585428 and rs4809960 polymorphisms, related to vitamin D degradation, were significantly associated with overall cancer risk.¹¹Zhu M, Qiu S et al. The associations between CYP24A1 polymorphisms and cancer susceptibility: a meta-analysis and trial sequential analysis. Pathology, Research and Practice. 2018 Jan;214(1):53-63.
• A link has been shown among gene polymorphisms FokI, BsmI, TaqI, and ApaI and tumorigenesis¹²Rai V, Abdo J, Agrawal S, Agrawal DK. Vitamin D receptor polymorphism and cancer: an update. Anticancer Research. 2017 Aug;37(8):3991-4003. or cancer risk.¹³Gnagnarella P, Pasquali E et al. Vitamin D receptor polymorphism FokI and cancer risk: a comprehensive meta-analysis. Carcinogenesis. 2014 Sep;35(9):1913-9.
• VDR Cdx-2 polymorphism (rs11568820) is associated with an increased cancer risk, particularly in American-Africans, colorectal, and ovarian cancers.¹⁴Dai ZM, Fei YL et alJ. Association of vitamin D receptor Cdx-2 polymorphism with cancer risk: a meta-analysis. Medicine (Baltimore). 2015 Aug;94(33):e1370.
• The BsmI B allele shows a weak effect in reducing cancer risk at any site, especially of the skin. ¹⁵Raimondi S, Pasquali E et al. BsmI polymorphism of vitamin D receptor gene and cancer risk: a comprehensive meta-analysis. Mutation Research. 2014 Nov;769:17-34.
• An overall increased risk of cancer is associated with Cdx2 SNP and a specific higher risk of colorectal cancer associated with the TaqI polymorphism.¹⁶Serrano D, Gnagnarella P, Raimondi S, Gandini S. Meta-analysis on vitamin D receptor and cancer risk: focus on the role of TaqI, ApaI, and Cdx2 polymorphisms. European Journal of Cancer Prevention. 2016 Jan;25(1):85-96.
• B allele of BamI polymorphism was a risk factor for cancer susceptibility. T allele of TaqI polymorphism was a risk factor for oral, breast, and basal cell cancer and a protective factor for prostate cancer. F allele of FokI polymorphism was a risk factor for ovarian and skin cancer and a protective factor for glioma. Finally, a allele of ApaI polymorphism was a risk factor for basal cell cancer in the Asian population.¹⁷Xu Y, He B et al. Systematic review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Tumour Biology. 2014 May;35(5):4153-69.

Breast cancer

• The rs4809960 SNP, related to vitamin D degradation, significantly decreased the risk of breast cancer.¹⁸Zhu M, Qiu S et al. The associations between CYP24A1 polymorphisms and cancer susceptibility: a meta-analysis and trial sequential analysis. Pathology, Research and Practice. 2018 Jan;214(1):53-63.
• VDR Bsm1, Apa1, Fok1, and Poly (A) gene polymorphisms may be susceptible for breast cancer development.¹⁹Iqbal MUN, Khan TA. Association between vitamin D receptor Cdx2, Fok1, Bsm1, Apa1, Bgl1, Taq1, and Poly (A) gene polymorphism and breast cancer: a systematic review and meta-analysis. Tumour Biology. 2017 Oct;39(10):1010428317731280; Zhao Z, Cai W, Xing J, Zhao C. Lower vitamin D levels and VDR variants are risk factors for breast cancer: an updated meta-analysis. Nucleosides, Nucleotides & Nucleic Acids. 2023;42(1):17-37; Lee YH, Song GG. Vitamin D receptor FokI, BsmI, ApaI, and TaqI polymorphisms and the susceptibility to breast cancer: a meta-analysis. Neoplasma. 2014;61(5):607-16; Zhang K, Song L. Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies. PLoS One. 2014 Apr 25;9(4):e96125. But an older meta-analysis found that VDR polymorphism (Fok1, Bsm1, Taq1, and Apa1) were not associated with the risk of breast cancer in the general population as well as the Caucasian population,²⁰Lu D, Jing L, Zhang S. Vitamin D receptor polymorphism and breast cancer risk: a meta-analysis. Medicine (Baltimore). 2016 May;95(18):e3535. while another meta-analysis found that the roles that Fok1, Apa1, Cdx2 and Poly-A polymorphisms play in breast cancer risk are negligible, with Bsm1 and Taq1 as possible exceptions.²¹Huang QQ, Liao YY, Ye XH, Fu JJ, Chen SD. Association between VDR polymorphisms and breast cancer: an updated and comparative meta-analysis of crude and adjusted odd ratios. Asian Pacific Journal of Cancer Prevention. 2014;15(2):847-53.

Colorectal cancer

• The BsmI variant was significantly correlated with a lower risk of colorectal cancer,²²Bai YH, Lu H et al. Vitamin D receptor gene polymorphisms and colorectal cancer risk: a systematic meta-analysis. World Journal of Gastroenterology. 2012 Apr 14;18(14):1672-9. especially in the Caucasian population. Cdx-2 polymorphism was found to be associated with decreased CRC risk among Africans.²³Yang M, Ji W et al. Association of vitamin D receptor polymorphisms with colorectal cancer susceptibility: a systematic meta-analysis. Medicine (Baltimore). 2023 Jan 6;102(1):e32575.
• Benefits from vitamin D₃ supplementation for the prevention of advanced colorectal adenomas may vary according to vitamin D receptor genotype.²⁴Barry EL, Peacock JL et al. Vitamin D receptor genotype, vitamin D₃ supplementation, and risk of colorectal adenomas: a randomized clinical trial. Journal of the American Medical Association Oncology. 2017 May 1;3(5):628-635.
• The role of VDR FokI polymorphism may differ based on the type and severity of colorectal disease.²⁵Cho YA, Lee J et al. Vitamin D receptor FokI polymorphism and the risks of colorectal cancer, inflammatory bowel disease, and colorectal adenoma. Scientific Reports. 2018 Aug 27;8(1):12899.
• No evidence showed that TaqI polymorphisms were significantly associated with susceptibility to colorectal cancer.²⁶Sheng S, Chen Y, Shen Z. Correlation between polymorphism of vitamin D receptor TaqI and susceptibility to colorectal cancer: a meta-analysis. Medicine (Baltimore). 2017 Jun;96(26):e7242.
• The rs964293 variant modifies the association between combined estrogen–progestogen (E+P) hormone preparations and colorectal cancer risk.²⁷Garcia-Albeniz X, Rudolph A et al. CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk. British Journal of Cancer. 2016 Jan 19;114(2):221-9.

Gastrointestinal cancer

• FokI rs2228570 and Taq1 rs731236 polymorphisms of the vitamin D receptor gene might be linked to the odds of gastric cancer.²⁸Guan M, Wang Y. Common variants of vitamin D receptor gene polymorphisms and risk of gastric cancer: a meta-analysis. Medicine (Baltimore). 2024 Aug 30;103(35):e39527.
• VDR rs7975232, VDR rs2228570, VEGF rs699947, VEGF rs3025039, IL-18 rs1946518, and MBL rs7096206 polymorphisms may confer susceptibility to hepatocellular carcinoma in certain populations.²⁹Quan Y, Yang J, Qin T, Hu Y. Associations between twelve common gene polymorphisms and susceptibility to hepatocellular carcinoma: evidence from a meta-analysis. World Journal of Surgical Oncology. 2019 Dec 12;17(1):216.

Gynecologic cancer

Ovarian cancer is listed separately.

• VDR ApaI (rs7975232) and VDR BsmI (rs1544410) polymorphisms are correlated with susceptibility to PCOS in the Asian population and VDR TaqI (rs731236), VDR FokI (rs2228570), VDR Tru9I (rs757343) did not reveal a relationship with the PCOS susceptibility.³⁰Shi XY, Huang AP, Xie DW, Yu XL. Association of vitamin D receptor gene variants with polycystic ovary syndrome: a meta-analysis. BMC Medical Genetics. 2019 Feb 14;20(1):32.
• Polycyctic ovary syndrome (PCOS) risk was significantly associated with VDR gene ApaI polymorphism.³¹Liang F, Ren N et al. A meta-analysis of the relationship between vitamin D receptor gene ApaI polymorphisms and polycystic ovary syndrome. Advances in Clinical and Experimental Medicine. 2019 Feb;28(2):255-262.
• The F variant reduces the risk of cancer by 4%. This effect is particularly evident in female sex-associated cancers, but it is not observed in non-sex-associated cancers.³²Laczmanski L, Lwow F et al. Association of the vitamin D receptor FokI gene polymorphism with sex- and non-sex-associated cancers: a meta-analysis. Tumour Biology. 2017 Oct;39(10):1010428317727164.
• The VDR rs2228570 polymorphism increased the risk of ovarian cancer in Caucasian populations in a dominant genetic model.³³Chen H, Zhu J. Vitamin D receptor rs2228570 polymorphism and susceptibility to ovarian cancer: an updated meta-analysis. Journal of Obstetrics and Gynaecology Research. 2018 Mar;44(3):556-565.
• The FokI and BsmI VDR gene polymorphisms may be significantly associated with gynecological cancers.³⁴Mun MJ, Kim TH, Hwang JY, Jang WC. Vitamin D receptor gene polymorphisms and the risk for female reproductive cancers: a meta-analysis. Maturitas. 2015 Jun;81(2):256-65.

Head and neck cancer

• Polymorphisms are associated variably with the anatomical site of cancer: oral cancer in ApaI and BsmI, and unspecified subsites of head and neck cancer in TaqI.³⁵Ferri CA, de Lima VJ, Dos Santos PK, Rados PV, Visioli F. Is vitamin D receptor (VDR) polymorphism associated with head and neck cancer risk? A systematic review and meta-analysis. Journal of Oral Pathology & Medicine. 2024 Jul;53(6):341-357.

Kidney cancer

• The vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype are associated with renal cell carcinoma risk.³⁶Zhou T, Li H et ak. Association of methylenetetrahydrofolate reductase, vitamin D receptor, and interleukin-16 gene polymorphisms with renal cell carcinoma risk. Technology in Cancer Research & Treatment. 2019 Jan 1;18:1533033819859413.
• ApaI gene polymorphism and Fok1 FF genotype were associated with renal cell carcinoma susceptibility in Asians.³⁷Lin ZJ, Zhang XL et al. Relationship between vitamin D receptor gene polymorphism and renal cell carcinoma susceptibility. Journal of Cancer Research and Therapeutics. 2018;14(4):820-825.
• The ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians.³⁸Ou C, Zhao HL, Zhu B, Huang LS, Li PZ, Lao M. Association of vitamin D receptor gene polymorphism with the risk of renal cell carcinoma: a meta-analysis. Journal of Receptor and Signal Transduction Research. 2014 Dec;34(6):463-8.
• The VDR BsmI polymorphism was not found to be associated with renal cell carcinoma risk, although subgroup analysis revealed a significant association with renal cell carcinoma risk in Asians. No significant association was found between renal cell carcinoma risk and either FokI or TaqI polymorphisms in different models and populations.³⁹Meng F, Ma P et al. The association between VDR polymorphisms and renal cell carcinoma susceptibility: a meta-analysis. Tumour Biology. 2014 Jun;35(6):6065-72.

Lung cancer

• The VDR Bsm1 and Cdx2 polymorphisms decreased lung cancer risk, while the Taq1 polymorphism increased lung cancer risk. The AA genotype of the Apa1 and Bsm1 variants were protective factors in Asian populations, whereas the Fok1 and Taq1 polymorphisms were risk factors for lung cancer in Asian populations.⁴⁰Duan GQ, Zheng X et al. The association between VDR and GC polymorphisms and lung cancer risk: a systematic review and meta-analysis. Genetic Testing and Molecular Biomarkers. 2020 May;24(5):285-295.
• Lung cancer risk varies by vitamin D receptor (VDR) genetic polymorphism.⁴¹Yu ZH, Chen M, Zhang QQ, Hu X. The association of vitamin D receptor gene polymorphism with lung cancer risk: an update meta-analysis. Combinatorial Chemistry & High Throughput Screening. 2018;21(10):704-710.
• Reference SNP rs6068816 in CYP24A1, rs1544410 and rs731236 in VDR and rs7041 in GC were statistically significant in relation to reduction in NSCLC risk.⁴²Wu X, Cheng J, Yang K. Vitamin D-related gene polymorphisms, plasma 25-hydroxy-vitamin d, cigarette smoke and non-small cell lung cancer (NSCLC) risk. International Journal of Molecular Sciences. 2016;17.
• B allele bb genotype t allele and TT genotype were associated with lung cancer risk in overall populations. AA genotype, B allele, BB genotype and bb genotype were associated with the risk of lung cancer in Asians. Furthermore, bb genotype t allele and TT genotype was associated with lung cancer risk in Caucasians.⁴³Zhong H, Zhou R et al. Association of vitamin D receptor gene polymorphism with the risk of lung cancer: a meta-analysis. Journal of Receptor and Signal Transduction Research. 2014 Dec;34(6):500-5.
• The polymorphisms of VDR BsmI and TaqI play protective roles in the lung carcinogenesis, particularly among smokers.⁴⁴Fu Y, Li J, Zhang Y. Polymorphisms in the vitamin D receptor gene and the lung cancer risk. Tumour Biology. 2014 Feb;35(2):1323-30.

Melanoma and other skin cancers

• The VDR variants FokI, ApaI and BsmI may influence the susceptibility to developing melanoma.⁴⁵Birke M, Schöpe J, Wagenpfeil S, Vogt T, Reichrath J. Association of vitamin D receptor gene polymorphisms with melanoma risk: a meta-analysis and systematic review. Anticancer Research. 2020 Feb;40(2):583-595; Hou W, Wan X, Fan J. Variants Fok1 and Bsm1 on VDR are associated with the melanoma risk: evidence from the published epidemiological studies. BMC Genetics. 2015 Feb 11;16:14; Lee YH, Gyu Song G. Vitamin D receptor FokI, BsmI, TaqI, ApaI, and EcoRV polymorphisms and susceptibility to melanoma: a meta-analysis. Journal of BUON. 2015 Jan-Feb;20(1):235-43.
• Participants with rs2228570 and rs927650 recessive genotypes had a decreased risk of squamous cell carcinoma (SCC), plus a lower SCC risk in rs1544410 recessive genotypes, while rs7975232 and rs739837 recessive genotypes were associated with a decreased BCC risk.⁴⁶Von Schuckmann LA, Law MH, Montgomery GW, Green AC, Van Der Pols JC. Vitamin D pathway gene polymorphisms and keratinocyte cancers: a nested case-control study and meta-analysis. Anticancer Research. 2016 May;36(5):2145-52.
• No significant association was observed between the Bsm1 polymorphism and skin cancer risk. The current meta-analysis shows that Fok1, Taq1 and Apa1 may be the susceptibility biomarker for skin cancer in Caucasians.⁴⁷Zhao XZ, Yang BH, Yu GH, Liu SZ, Yuan ZY. Polymorphisms in the vitamin D receptor (VDR) genes and skin cancer risk in European population: a meta-analysis. Archives of Dermatological Research. 2014 Aug;306(6):545-53.

Myeloma

• Vitamin D receptor gene polymorphisms including ApaI, BsmI, TaqI, and FokI are associated with MM risk in Asian populations.⁴⁸Lyu C, Yin X, Li Z, Wang T, Xu R. Vitamin D receptor gene polymorphisms and multiple myeloma: a meta-analysis. Clinical and Experimental Medicine. 2024 Jun 4;24(1):118. 
• No polymorphisms in VDR were found to be strongly related to risk for people of European ancestry.⁴⁹Cheah S, English DR, Harrison SJ, Vajdic CM, Giles GG, Milne RL. Sunlight, vitamin D, vitamin D receptor polymorphisms, and risk of multiple myeloma: a systematic review. Cancer Epidemiology. 2023 Dec;87:102488.

Ovarian cancer

• VDR rs2228570 (FokI) and ApaI polymorphisms are associated with risk of ovarian cancer in Caucasians.⁵⁰Li S, Xu H, Li SC, Qi XQ, Sun WJ. Vitamin D receptor rs2228570 polymorphism and susceptibly to ovarian cancer: a meta-analysis. Tumour Biology. 2014 Feb;35(2):1319-22; Xu H, Li S, Qiu JQ, Gao XL, Zhang P, Yang YX. The VDR gene FokI polymorphism and ovarian cancer risk. Tumour Biology. 2013 Dec;34(6):3309-16; Song GG, Lee YH. Vitamin D receptor FokI, BsmI, ApaI, and TaqI polymorphisms and susceptibility to ovarian cancer: a meta-analysis. Immunological Investigations. 2013;42(7):661-72; Liu Y, Li C et al. Polymorphisms in the vitamin D receptor (VDR) and the risk of ovarian cancer: a meta-analysis. PLoS One. 2013 Jun 24;8(6):e66716.
• Vitamin D receptor BsmI G/A gene variant might be a moderate risk factor of OC development in the European population instead of North America or Asian population.⁵¹Qin X, Lu Y, Qin A et al. Vitamin D receptor BsmІ polymorphism and ovarian cancer risk: a meta-analysis. International Journal of Gynecological Cancer. 2013 Sep;23(7):1178-83.
• There is no association between VDR BsmI polymorphism and susceptibility to ovarian cancer in Caucasians.⁵²Zhang Y, Tong SC et al. Meta-analysis of the relation between vitamin D receptor gene BsmI polymorphism and susceptibility to ovarian cancer. Tumour Biology. 2013 Dec;34(6):3317-21.

Pancreatic cancer

• The VDR rs2585428 SNP significantly decreased the risk of pancreas cancer.⁵³Zhu M, Qiu S et al. The associations between CYP24A1 polymorphisms and cancer susceptibility: a meta-analysis and trial sequential analysis. Pathology, Research and Practice. 2018 Jan;214(1):53-63.

Prostate cancer

• A significant association is seen between VDR rs731236 and prostate cancer risk in Asians and African Americans, but rs1544410 was not associated with prostate cancer under three genetic models.⁵⁴Liu S, Cai H et al. Association of VDR polymorphisms (Taq I and Bsm I) with prostate cancer: a new meta-analysis. Journal of International Medical Research. 2017 Feb;45(1):3-10.
• One meta-analysis concluded that “the VDR Fok I polymorphism might be capable of causing PCa susceptibility”⁵⁵Kang S, Zhao Y et al. Association of vitamin D receptor Fok I polymorphism with the risk of prostate cancer: a meta-analysis. Oncotarget. 2016 Nov 22;7(47):77878-77889. but another came to the opposite conclusion: “the VDR BsmI and FokI polymorphisms are not related to prostate cancer risk.”⁵⁶Guo Z, Wen J et al. Lack of association between vitamin D receptor gene FokI and BsmI polymorphisms and prostate cancer risk: an updated meta-analysis involving 21,756 subjects. Tumour Biology. 2013 Oct;34(5):3189-200. A third meta-analysis concluded “VDR FokI allele F might be a protective factor for European and American Caucasians.”⁵⁷Cao J, Li X, Hou Q, Li R, Luo R. [Polymorphism of vitamin D receptor gene FokI and susceptibility of prostatic cancer: a meta-analysis]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2012 Dec;37(12):1215-20. Chinese. The differences may be due to the study populations. 
• VDR Cdx2 and ApaI polymorphisms are not associated with prostate cancer.⁵⁸Wang K, Wu G, Li J, Song W. Role of vitamin D receptor gene Cdx2 and Apa1 polymorphisms in prostate cancer susceptibility: a meta-analysis. BMC Cancer. 2016 Aug 23;16(1):674.

Thyroid cancer

• Vitamin D receptor polymorphisms are not associated with increased susceptibility to differentiated thyroid cancer.⁵⁹Maciejewski A, Lacka K. Vitamin D-related genes and thyroid cancer-a systematic review. International Journal of Molecular Sciences. 2022 Nov 7;23(21):13661.

Body terrain factors

• Genetic variants associated with low plasma 25(OH)D concentrations are associated with type 2 diabetes.⁶⁰Afzal S, Brøndum-Jacobsen P, Bojesen SE, Nordestgaard BG. Vitamin D concentration, obesity, and risk of diabetes: a Mendelian randomisation study. Lancet Diabetes and Endocrinology. 2014 Apr;2(4):298-306. 
• Compared with the controls (noncancer patients), heterozygote and dominant models with the VDR rs1544410 (BsmI) is likely the best genetic model for detecting the risk of ovarian cancer in Caucasian patients.⁶¹Li J, Li B et al. Do genetic polymorphisms of the vitamin D receptor contribute to breast/ovarian cancer? A systematic review and network meta-analysis. Gene. 2018 Nov 30;677:211-227.
• Vitamin D and its receptor VDR contribute to the protective process of probiotics.⁶²Shang M, Sun J. Vitamin D/VDR, probiotics, and gastrointestinal diseases. Current Medicinal Chemistry. 2017;24(9):876-887.
• The association between insulin resistance-related diseases and VDR ApaI, BsmI, FokI variant was more obvious in dark-pigmented Caucasians and Asians but not in Caucasians with white skin.⁶³Han FF, Lv Y et al. VDR gene variation and insulin resistance related diseases. Lipids in Health and Disease. 2017 Aug 19;16(1):157.

Side effects

Regarding aromatase inhibitor-induced arthralgia (AIA), one study found that “vitamin D levels were not significantly associated with development of AIA; however, patients with the Fok-I VDR variant genotype were more likely to have a significant reduction in IL-1β level, and less likely to develop AIA.”⁶⁴Niravath P, Chen B et al. Vitamin D levels, vitamin D receptor polymorphisms, and inflammatory cytokines in aromatase inhibitor-induced arthralgias: an analysis of CCTG MA.27. Clinical Breast Cancer. 2018 Feb;18(1):78-87.

Vitamin D-binding protein

An analysis of 28 studies found a borderline decrease in cancer risk for subjects with high compared with low levels of vitamin D-binding protein.⁶⁵Tagliabue E, Raimondi S, Gandini S. Meta-analysis of vitamin D-binding protein and cancer risk. Cancer Epidemiology, Biomarkers & Prevention. 2015 Nov;24(11):1758-65.

Preclinical evidence 

This summarizes notable preclinical evidence; clinical evidence is listed in How can vitamin D help you? What the research says ›

Improving treatment outcomes

• Vitamin D enhanced antitumor activity of docetaxel in an androgen-independent prostate cancer cell line in a preclinical study.⁶⁶Ting HJ, Hsu J, Bao BY et al. Docetaxel-induced growth inhibition and apoptosis in androgen independent prostate cancer cells are enhanced by 1alpha, 25- dihydroxyvitamin D3. Cancer Letters. 2007;247:122–9.
• Calcitriol enhanced activity of docetaxel, paclitaxel, and platinum compounds in preclinical studies of prostate cancer.⁶⁷Beer TM, Hough KM et al. Weekly high dose calcitriol and docetaxel in advanced prostate cancer. Seminars in Oncology. 2001;28(4 Suppl 15):49–55. 
• Vitamin D₃ with or without docetaxel was similarly effective in reducing CD34(+) cell levels within the spleen, lymph nodes, and murine squamous cell carcinoma model tumor.⁶⁸Young MR, Lathers DM. Combination docetaxel plus vitamin D(3) as an immune therapy in animals bearing squamous cell carcinomas. Otolaryngology—Head and Neck Surgery. 2005;133:611–8. 
• Vitamin D signaling inhibits the expression of the tumor progression gene Id1, reducing breast cancer metastasis in preclinical studies.⁶⁹Williams JD, Aggarwal A et al. Tumor autonomous effects of vitamin D deficiency promote breast cancer metastasis. Endocrinology. 2016 Apr;157(4):1341-7.
• Vitamin D metabolism has been identified as a key process in the development of hepatocellular carcinoma.⁷⁰Walakira A, Skubic C et al. Integrative computational modeling to unravel novel potential biomarkers in hepatocellular carcinoma. Computers in Biology and Medicine. 2023 Jun;159:106957.

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