Loading...
 
Toggle Health Problems and D

Colon Cancer protects itself by changing the VDR and CYP3A4 genes – Dec 2022


Correlated downregulation of VDR and CYP3A4 in colorectal cancer

Mol Biol Rep . 2022 Dec 5. doi: 10.1007/s11033-022-08141-2 PDF is behind a paywall
Hossein Sadeghi 1 , Veys Hashemnia 2 , Ehsan Nazemalhosseini-Mojarad 3 , Mohammad Reza Ghasemi 2 , Reza Mirfakhraie 4 5

Background: The evidence obtained from experimental studies suggests the tumor-suppressive effects of vitamin D by controlling the differentiation, proliferation, and apoptosis in cancerous cells. Furthermore, the deregulation of genes involved in vitamin D metabolism has been reported in several types of cancer.

Methods: In the present study, we investigated the expression level of vitamin D metabolic pathway genes, including VDR, CYP3A4, RXRa, and GC, in colorectal cancer (CRC) samples compared with the adjacent tissues by using quantitative RT-PCR.

Results: The results indicated significant downregulation of CYP3A4 and VDR genes in CRC tissues compared with the adjacent control tissues (p < 0.01). RXRA and GC expression levels did not show any significant alteration among the studied samples. Moreover, a positive correlation was observed between the expression level of CYP3A4 and VDR genes (p < 0.0001). ROC curve analysis also revealed the potential diagnostic power of CYP3A4 and VDR genes in CRC samples.

Conclusion: Reduction in the expression of both CYP3A4 and VDR plays an important role in CRC due to the possible impairment in vitamin D metabolism. Further studies concerning the relationship between the expression of these genes and colorectal cancer pathogenesis and treatment are recommended.


Butyrate upregulates VDR in the colon

14th activator of the Vitamin D Receptor – Butyrate (from gut bacteria, or supplement)


Vitamin D Life -Some diseases reduce vitamin D getting to blood or cells

Some diseases restrict vitamin D by changing gene activation,
   by one or more of the following

  • Restrict conversion of light into vitamin D in the skin
  • Restrict oral absorption in the gut
  • Restrict semi-activation in the liver
  • Restrict free semi-activated vitamin D from getting to the kidneys
  • Restrict full activation in the kidneys
  • Restrict semi and fully activation in the cells
  • Restrict activated Vitamin D from entering cell mitochondria (VDR)
  • Destroy the vitamin D before it gets to the cells

Some diseases restrict vitamin D without changing genes

  • The disease just uses/consumes the vitamin D
  • The disease upsets the gut, which reduces bioavailability of oral form
    • unless a gut-friendly form is used

References



Vitamin D Life - Vitamin D Receptor deactivated by some health problems - many studies


Vitamin D Life - Genetics chart shows the vitamin D genes

in Visio for 2023

CYP3A4 (7 as of Dec 2022)


Vitamin D Life - 13 studies in both categories Colon Cancer and Vitamin D Receptor

This list is automatically updated


81 Vitamin D Life VDR pages have CANCER in title (as of Dec 2022)

This list is automatically updated

Items found: 86
Title Modified
Vitamin D Receptor (Cancers OR Viruses) - many studies 02 Mar, 2024
Oral Cancer and Vitamin D and VDR - several studies 11 Feb, 2024
Breast Cancer risk reduced if consume butyrate - Dec 2023 23 Jan, 2024
An activated Vitamin D Receptor fights Autoimmune Diseases, Infections, Cancers, etc. – Dec 2023 13 Jan, 2024
Cervical Cancer is prevented by Vitamin D, and treated if caught early (genes are important) – May 2023 27 May, 2023
Colon Cancer protects itself by changing the VDR and CYP3A4 genes – Dec 2022 06 Dec, 2022
Breast cancer spreads to bone if poor vitamin D Receptor (no surprise) – Oct 2022 31 Oct, 2022
2X more Thyroid Cancer malignancy if less than 15 ng of vitamin D – June 2012 16 Sep, 2022
Cancers are associated with low vitamin D, poor vaccination response and perhaps poor VDR – July 2022 15 Aug, 2022
Poor prognosis of solid childhood cancers 14.7 X more likely with a poor Vitamin D Receptor – July 2022 27 Jul, 2022
Breast Cancer, Vitamin D, and genes – Welsh Nov 2021 09 Feb, 2022
How cancer is fought by Vitamin D (Ovarian this time) - Feb 2020 01 Nov, 2021
Lung Cancer is up to 7 X more deadly if poor vitamin D genes – Oct 2021 25 Oct, 2021
Cancers and Vitamin D Receptors, including change with race – Feb 2021 24 Oct, 2021
Breast Cancer reduces receptor and thus blocks Vitamin D to the cells – several studies 18 Oct, 2021
After lactation Vitamin D levels are low, increased risk of Breast Cancer, vitamin D should decrease risk – Aug 2021 20 Aug, 2021
Breasts process Vitamin D and change gene activation, might prevent breast cancer if given more Vit. D – July 2021 10 Jul, 2021
Oral Cancers - increased risk if low vitamin D or poor vitamin D genes 22 Jan, 2021
Colon cancer risk increases 30X if you have the worst vitamin D receptor mutation – Jan 2021 15 Jan, 2021
Book: Sunlight, UV, Vitamin D and Receptor, Skin and other Cancers - Dec 2020 09 Dec, 2020
Colorectal Cancer Patients 2.4 X more likely to have poor Vitamin D receptors (less D to cells) – April 2020 02 May, 2020
Colorectal cancer linked to poor Vitamin D Receptor (yet again) – Jan 2020 22 Jan, 2020
8 ways that Cancer might be prevented by Vitamin D - June 2019 26 Dec, 2019
Liver Cancer – higher risk if poor genes (Vitamin D receptor etc) – meta-analysis Dec 2019 14 Dec, 2019
Prostate Cancer associated with various genes, including Vitamin D Receptor and CYP24A1 – Nov 2019 15 Nov, 2019
Risk of Cancer increased if poor Vitamin D Receptor – meta-analysis of 73 studies Jan 2016 09 Nov, 2019
Cancer is leading cause of death - Vitamin D and Receptor activators help 09 Nov, 2019
Melanoma cancer growth slowed by increased Vitamin D Receptor (yet again) – Oct 2019 06 Nov, 2019
Breast cancer associated with Vitamin D Receptor (14th study) – Oct 2019 19 Oct, 2019
Colorectal Cancer risk increases when genes reduce the vitamin D levels – Aug 2019 23 Aug, 2019
Breast Cancer death 1.8 X more likely if poor Vitamin D Receptor – April 2019 29 Jul, 2019
Multiple Myeloma (blood cell cancer) treated by vitamin D - many studies 14 Jun, 2019
Blood cell cancer is associated with a 3X worse Vitamin D Receptor – June 2019 14 Jun, 2019
Lung Cancer more likely if poor Vitamin D Receptor – meta-analysis June 2019 13 Jun, 2019
After breast cancer treatment 4,000 IU of Vitamin D was not enough to help if have poor Vitamin D receptor – June 2019 04 Jun, 2019
Effects of Resveratrol against Lung Cancer in mice – Nov 2017 28 Apr, 2019
The Role of Resveratrol in Cancer Therapy – Dec 2017 27 Apr, 2019
Good Vitamin D receptor reduced bladder cancer and cisplatin deaths – April 2019 11 Apr, 2019
A poor Vitamin D Receptor is associated with many cancers (oral cancer in this case) – Jan 2019 26 Mar, 2019
Breast Cancer and Vitamin D review – March 2018 17 Mar, 2019
Overview of Vitamin D Actions in Cancer – 31 page chapter in a book – 2018 15 Mar, 2019
Women with Breast Cancer were 16.9 times more likely to have a poor Vitamin D Receptor – Jan 2019 11 Feb, 2019
Risks of Colorectal Cancer, IBD, etc slightly increased if poor Vitamin D Receptor – Aug 2018 09 Dec, 2018
Ovarian Cancer risk reduced if higher vitamin D, more UVB, or better vitamin D receptor – Nov 2018 10 Nov, 2018
Cancer treatment by Vitamin D sometimes is restricted by genes – Oct 2018 01 Nov, 2018
Brain cancer in 175 countries related to low UVB and low vitamin D – Oct 2010 03 Oct, 2018
Pancreatic Cancer – live a year longer if have high vitamin D and good Vitamin D Receptor – Aug 2018 15 Aug, 2018
Endometriosis, Endometrial Cancer, and poor Vitamin D or Receptor – Aug 2018 08 Aug, 2018
Risk of colon cancer increases in mice with no Vitamin D receptor in colon - July 2018 07 Jul, 2018
Vitamin D receptor is essential for both normal and cancerous cells in the lab – June 2018 16 Jun, 2018
Active Vitamin D reduces Ovarian Cancer stem cells growth by 4X (via Vitamin D receptor in lab rat) – March 2018 28 Mar, 2018
Two chemicals increase the Vitamin D receptor and decrease the growth of breast cancer cells in the lab - March 2018 17 Mar, 2018
Ovarian Cancer in Asia is 1.5 X more likely if poor Vitamin D receptor – meta-analysis Dec 2017 14 Dec, 2017
Nonmelanoma Skin Cancer 2X more likely if poor Vitamin D Receptor – Oct 2017 19 Oct, 2017
Cancer and the Vitamin D Receptor, a primer – Sept 2017 01 Oct, 2017
Thyroid Cancer rate has increased 3X in 3 decades, Vitamin D Receptor decreases, Calcium increases – Aug 2017 26 Aug, 2017
Advanced Colon Cancer risk is doubled or halved with 1000 IU of Vitamin D, depends on Vitamin D Receptors – RCT May 2017 19 Aug, 2017
Cancer risks and Vitamin D Receptors – association is unclear – 2017 19 Aug, 2017
Increased Breast Cancer metastasis if low vitamin D or poor VDR – Feb 2016 09 Aug, 2017
Colon Cancer survival 3.1 X less likely if poor Vitamin D Receptor – Aug 2017 02 Aug, 2017
Lung Cancer patients were 2.4 times more likely to have a poor Vitamin D Receptor gene – July 2017 27 Jul, 2017
Pancreatic Cancer massively deregulates the local Vitamin D receptors and CPY24A1 – July 2014 25 Jul, 2017
Gastric Cancer 2.7 X more likely if poor Vitamin D Receptor (Chinese) – 2015 15 Jun, 2017
Skin Cancers, Vitamin D, Vitamin D Receptor and Genes – Jan 2015 17 Mar, 2017
Prostate cancer in black men is 1.6 times more likely if a poor Vitamin D Receptor – Feb 2017 06 Mar, 2017
2X more likely to survive a form of esophageal cancer in China if have good vitamin D receptor – Feb 2017 04 Mar, 2017
Urinary Bladder Cancer survival is associated with vitamin D receptor: 14 months vs 53 months – Oct 2015 02 Mar, 2017
Vitamin D receptor as a target for breast cancer therapy (abstract only) – Feb 2017 01 Mar, 2017
Ovarian Cancer 5.8 X more likely if both low vitamin D and Fok1 gene change – May 2013 27 Feb, 2017
Vitamin D receptor may suppress skin cancer – Dec 2013 27 Jan, 2017
Aggressive Prostate Cancer in blacks with low vitamin D – 7X more likely if added Calcium – Jan 2017 28 Dec, 2016
Breast Cancer was 4.6 times more likely if have a poor Vitamin D Receptor – Dec 2016 06 Dec, 2016
Vitamin D, Vitamin D Receptor and Cancer – Nov 2016 05 Dec, 2016
High PSA readings with Prostate Cancer 4 times more likely if poor Vitamin D receptor – March 2016 14 Nov, 2016
2X less prostate cancer in A-A with low Calcium is due vitamin D receptor gene – July 2013 14 Nov, 2016
Vitamin D receptor polymorphisms are risk factors for various cancers – meta-analysis Jan 2014 12 Nov, 2016
10 percent of colon cancer linked to Vitamin D Receptor – meta-analysis April 2012 23 Sep, 2016
Vitamin D Receptor role in Autoimmune Diseases and or cancers – Nov 2013 17 Mar, 2016
Skin cancer 20 percent more likely with some Vitamin D receptor gene polymorphisms – Oct 2015 06 Jan, 2016
Pancreatic Cancer treatment by calcipotriol (a synthetic vitamin D) improves outcome by 57 percent – Sept 2014 13 Dec, 2015
Poor Bladder Cancer survival associated with poor Vitamin D receptor – Oct 2015 18 Oct, 2015
Increased risk of some female cancers if low vitamin D (due to genes) – meta-analysis June 2015 03 May, 2015
Free vitamin D (VDR) may be more important than total for bladder cancer – March 2013 06 Jan, 2014
Genes breast cancer and vitamin D receptor - Sept 2010 08 Jul, 2013
Breast Cancer incidence change by 40 percent with vitamin D receptor genes – Oct 2012 08 Jul, 2013
Vitamin D receptor in breasts and breast cancer vary with race – March 2013 08 Jul, 2013

Vitamin D Life - 7 studies in both categories Colon Cancer and Genetics

This list is automatically updated


Vitamin D Life - Cancer - Colon category contains


References

  1. Sawicki T, Ruszkowska M, Danielewicz A, Niedzwiedzka E, Arlukowicz T, Przybylowicz KE (2021) A review of colorectal cancer in terms of epidemiology, risk factors, development, symptoms and diagnosis. Cancers 13(9):2025 - DOI - PubMed - PMC
  2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin 71(3):209–249 - PubMed
  3. Rawla P, Sunkara T, Barsouk A (2019) Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Przeglad Gastroenterologiczny 14(2):89 - PubMed - PMC
  4. Dolatkhah R, Somi MH, Bonyadi MJ, Asvadi Kermani I, Farassati F, Dastgiri S (2015) Colorectal cancer in Iran: molecular epidemiology and screening strategies. J Cancer Epidemiol 2015:1–10 - DOI
  5. Hong SN (2018) Genetic and epigenetic alterations of colorectal cancer. Intest Res 16(3):327–337. https://doi.org/10.5217/ir.2018.16.3.327 - DOI - PubMed - PMC
  6. Jeon S-M, Shin E (2018) Exploring vitamin D metabolism and function in cancer. Exp Mol Med 50(4):1–14 - PubMed
  7. Boughanem H, Canudas S, Hernandez-Alonso P, Becerra-Tomás N, Babio N, Salas-Salvadó J et al (2021) Vitamin D intake and the risk of colorectal cancer: an updated meta-analysis and systematic review of case-control and prospective cohort studies. Cancers 13(11):2814 - DOI - PubMed - PMC
  8. Sadeghi H, Kamaliyan Z, Mohseni R, Sahebi U, Nazemalhosseini-Mojarad E, Aghaei N et al (2021) Dysregulation of vitamin D synthesis pathway genes in colorectal cancer: a case-control study. J Clin Lab Anal 35(2):e23617 - DOI - PubMed
  9. Afshan FU, Masood A, Nissar B, Chowdri NA, Naykoo NA, Majid M et al (2021) Promoter hypermethylation regulates vitamin D receptor (VDR) expression in colorectal cancer-A study from Kashmir valley. Cancer Genet 252–253:96–106. https://doi.org/10.1016/j.cancergen.2021.01.002 - DOI - PubMed
  10. Sadeghi H, Nazemalhosseini-Mojarad E, Sahebi U, Fazeli E, Azizi-Tabesh G, Yassaee VR et al (2021) Novel long noncoding RNAs upregulation may have synergistic effects on the CYP24A1 and PFDN4 biomarker role in human colorectal cancer. J Cell Physiol 236(3):2051–2057 - DOI - PubMed
  11. Sun H, Wang C, Hao M, Sun R, Wang Y, Liu T et al (2016) CYP24A1 is a potential biomarker for the progression and prognosis of human colorectal cancer. Hum Pathol 50:101–108. https://doi.org/10.1016/j.humpath.2015.11.008 - DOI - PubMed
  12. Yi C, Huang C, Wang H, Wang C, Dong L, Gu X et al (2020) Association study between CYP24A1 gene polymorphisms and cancer risk. Pathol Res Pract 216(1):152735. https://doi.org/10.1016/j.prp.2019.152735 - DOI - PubMed
  13. Egan JB, Thompson PA, Ashbeck EL, Conti DV, Duggan D, Hibler E et al (2010) Genetic polymorphisms in vitamin D receptor VDR/RXRA influence the likelihood of colon adenoma recurrence. Can Res 70(4):1496–1504 - DOI
  14. Huang G-L, Chen Q-X, Ma J-J, Sui S-Y, Wang Y-N, Shen D-Y (2019) Retinoic acid receptor a facilitates human colorectal cancer progression via Akt and MMP2 signaling. Onco Targets Ther 12:3087 - DOI - PubMed - PMC
  15. van Eijk M, Boosman RJ, Schinkel AH, Huitema ADR, Beijnen JH (2019) Cytochrome P450 3A4, 3A5, and 2C8 expression in breast, prostate, lung, endometrial, and ovarian tumors: relevance for resistance to taxanes. Cancer Chemother Pharmacol 84(3):487–499 - DOI - PubMed - PMC
  16. Wang Z, Schuetz EG, Xu Y, Thummel KE (2013) Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol 136:54–58 - DOI - PubMed
  17. Bouillon R, Schuit F, Antonio L, Rastinejad F (2020) Vitamin D binding protein: a historic overview. Front Endocrinol 10:910 - DOI
  18. Anic GM, Weinstein SJ, Mondul AM, Männistö S, Albanes D (2014) Serum vitamin D, vitamin D binding protein, and risk of colorectal cancer. PLoS ONE 9(7):e102966 - DOI - PubMed - PMC
  19. Poynter JN, Jacobs ET, Figueiredo JC, Lee WH, Conti DV, Campbell PT et al (2010) Genetic variation in the vitamin D receptor (VDR) and the vitamin D–binding protein (GC) and risk for colorectal cancer: results from the Colon Cancer Family Registry. Cancer Epidemiol Prev Biomark 19(2):525–536 - DOI
  20. Li Z, Jia Z, Gao Y, Xie D, Wei D, Cui J et al (2015) Activation of vitamin D receptor signaling downregulates the expression of nuclear FOXM1 protein and suppresses pancreatic cancer cell stemness. Clin Cancer Res 21(4):844–853 - DOI - PubMed
  21. Sana S, Kayani MA (2021) Role of Vitamin D deficiency and mRNA expression of VDR and RXR in haematological cancers. Mol Biol Rep 48(5):4431–4439 - DOI - PubMed
  22. Evans S, Nolla J, Hanfelt J, Shabahang M, Nauta RJ, Shchepotin IB (1998) Vitamin D receptor expression as a predictive marker of biological behavior in human colorectal cancer. Clin Cancer Res 4(7):1591–1595 - PubMed
  23. Saccone D, Asani F, Bornman L (2015) Regulation of the vitamin D receptor gene by environment, genetics and epigenetics. Gene 561(2):171–180 - DOI - PubMed
  24. Thomas M, Sylvester P, Newcomb P, Longman R (1999) Vitamin D receptor expression in colorectal cancer. J Clin Pathol 52(3):181–183 - DOI - PubMed - PMC
  25. Kacevska M, Robertson GR, Clarke SJ, Liddle C (2008) Inflammation and CYP3A4-mediated drug metabolism in advanced cancer: impact and implications for chemotherapeutic drug dosing. Expert Opin Drug Metab Toxicol 4(2):137–149 - DOI - PubMed
  26. Gervasini G, García-Martín E, Ladero JM, Pizarro R, Sastre J, Martínez C et al (2007) Genetic variability in CYP3A4 and CYP3A5 in primary liver, gastric and colorectal cancer patients. BMC Cancer 7(1):1–7 - DOI
  27. Kumarakulasingham M, Rooney PH, Dundas SR, Telfer C, Melvin WT, Curran S et al (2005) Cytochrome p450 profile of colorectal cancer: identification of markers of prognosis. Clin Cancer Res 11(10):3758–3765 - DOI - PubMed
  28. Dhaini HR, Thomas DG, Giordano TJ, Johnson TD, Biermann JS, Leu K et al (2003) Cytochrome P450 CYP3A4/5 expression as a biomarker of outcome in osteosarcoma. J Clin Oncol 21(13):2481–2485 - DOI - PubMed
  29. Pavek P, Pospechova K, Svecova L, Syrova Z, Stejskalova L, Blazkova J et al (2010) Intestinal cell-specific vitamin D receptor (VDR)-mediated transcriptional regulation of CYP3A4 gene. Biochem Pharmacol 79(2):277–287 - DOI - PubMed
  30. Roizen JD, Li D, O’Lear L, Javaid MK, Shaw NJ, Ebeling PR et al (2018) CYP3A4 mutation causes vitamin D-dependent rickets type 3. J Clin Investig 128(5):1913–1918 - DOI - PubMed - PMC
  31. Andersen SW, Shu XO, Cai Q, Khankari NK, Steinwandel MD, Jurutka PW et al (2017) Total and free circulating vitamin D and vitamin D-binding protein in relation to colorectal cancer risk in a prospective study of African Americans. Cancer Epidemiol Biomark Prev 26(8):1242–1247 - DOI
  32. Gibbs DC, Bostick RM, McCullough ML, Um CY, Flanders WD, Jenab M et al (2020) Association of prediagnostic vitamin D status with mortality among colorectal cancer patients differs by common, inherited vitamin D-binding protein isoforms. Int J Cancer 147(10):2725–2734 - DOI - PubMed - PMC
  33. Zhang F, Meng F, Li H, Dong Y, Yang W, Han A (2011) Suppression of retinoid X receptor alpha and aberrant ß-catenin expression significantly associates with progression of colorectal carcinoma. Eur J Cancer (Oxf, Engl: 1990). 47(13):2060–2067 - DOI
  34. Wasiewicz T, Piotrowska A, Wierzbicka J (2018) Antiproliferative activity of non-calcemic vitamin D analogs on human melanoma lines in relation to VDR and PDIA3 receptors. Int J Mol Sci 19(9):2583 - DOI - PubMed - PMC
  35. Ozawa S, Miura T, Terashima J, Habano W (2021) Cellular irinotecan resistance in colorectal cancer and overcoming irinotecan refractoriness through various combination trials including DNA methyltransferase inhibitors: a review. Cancer Drug Resist (Alhambra, Calif) 4(4):946–964
  36. Nallani SC, Goodwin B, Buckley AR, Buckley DJ, Desai PB (2004) Differences in the induction of cytochrome P450 3A4 by taxane anticancer drugs, docetaxel and paclitaxel, assessed employing primary human hepatocytes. Cancer Chemother Pharmacol 54(3):219–229 - DOI - PubMed




Created by admin. Last Modification: Tuesday March 12, 2024 15:30:39 GMT-0000 by admin. (Version 10)