Vitamin D and cancer

• 1000,000,000 people around the world.

•multi-system involvement.

• Vitamin D physiology..

http://www.precisionnutrition.com/wordpress/wp-content/uploads/2009/06/vitamin-d-metabolism.gif

vit. D physiology

http://www.nejm.org/doi/pdf/10.1056/NEJMra070553

Multi-system..but What about vit. D and cancer..??!!

• Evidence:• 1- pre-clinical.• 2- clinical.

1. Pre-clinical

• Action on :1- Cell ploferation.2- Apoptosis.3- Angiogenesis.4- Inflamation.

1- Cell proleferation :

• increase CDR-inhibetors• up-regulate IGFBP3

-M.J. Campbell, E. Elstner, S. Holden, M. Uskokovic, H.P. Koeffler, J. Mol. Endocrinol. 19 (1997) 15–27.-E.S. Yang, K.L. Burnstein, J. Biol. Chem. 278 (2003) 46862–46868.-B.J. Boyle, X.Y. Zhao, P. Cohen, D. Feldman, J. Urol. 165 (2001) 1319–1324.- L. Peng, P.J. Malloy, D. Feldman, Mol. Endocrinol. 18 (2004) 1109–1119.534

2- Apoptosis :

expression of P73 expression of Bcl-2 gene telomere activity autophagy the pro-apoptotic effect when administerwith

new anti-cancer medication (tricostatin A)

-Y. Ma, W.D. Yu, P.A. Hershberger, G. Flynn, R.X. Kong, D.L. Trump, C.S. Johnson, Mol. Cancer Ther. 7 (2008) 3047–3055.-S.E. Blutt, T.J. McDonnell, T.C. Polek, N.L. Weigel, Endocrinology 141 (2000) 10–17.-M. Hoyer-Hansen, S.P. Nordbrandt, M. Jaattela, Trends Mol. Med. 16 (2010) 295–302. -L. Pan, A.F. Matloob, J. Du, H. Pan, Z. Dong, J. Zhao, Y. Feng, Y. Zhong, B. Huang, J. Lu, FEBS J. 277 (2010) 989–999.

3- Angiogenesis:

expression of Tenascin-C, alpha-6 & beta-4. VEGF, IL-8 & COX-2.expressio of E-cadherin.

-M.J. Campbell, E. Elstner, S. Holden, M. Uskokovic, H.P. Koeffler, J. Mol. Endocrinol. 19 (1997) 15–27.-J.M. Gonzalez-Sancho, M. Alvarez-Dolado, A. Munoz, FEBS Lett. (1998) 225–228. -V. Sung, D. Feldman, Mol. Cell. Endocrinol. 164 (2000) 133–143.

• 4- inflamation: activation of NFKB pro-inflamatory cytokines (IL-1, IL-8)

B.Y. Bao, J. Yao, Y.F. Lee, Carcinogenesis 27 (2006) 1883–1893.

• Pre-clinical studies SUPPORT it.

• What about the clinical side..??!!

Clinical side

• 1- epidemiological studies.• 2- clinical trials.

Epidemiological studies:

• Retrospective case-control studies.• Prospective cohort studies.

S. Mocellin, Vitamin D and cancer: Deciphering the truth, Biochim. Biophys. Acta (2011), doi:10.1016/ j.bbcan.2011.07.001

Clinical trials

• cancer outcomes.• cancer prevention.

• Studies targeting cancer outcomes :

-T.M. Beer, C.W. Ryan, P.M. Venner, D.P. Petrylak, G.S. Chatta, J.D. Ruether, C.H. 643 Redfern, L. Fehrenbacher, M.N. Saleh, D.M. Waterhouse, M.A. Carducci, D. Vicario, 644 R. Dreicer, C.S. Higano, F.R. Ahmann, K.N. Chi, W.D. Henner, A. Arroyo, F.W. Clow, J.645 Clin. Oncol. 25 (2007) 669–674.

-S. Attia, J. Eickhoff, G. Wilding, D. McNeel, J. Blank, H. Ahuja, A. Jumonville, M. Eastman, D. Shevrin, M. Glode, D. Alberti, M.J. Staab, D. Horvath, J. Straus, R. 648 Marnocha, G. Liu, Clin. Cancer Res. 14 (2008) 2437–2443.

- M.K. Chadha, L. Tian, T. Mashtare, V. Payne, C. Silliman, E. Levine, M. Wong, C. Johnson, D.L. Trump, Cancer 116 (2010) 2132–2139.

Author Year Cancer Main finding

Beer 2007 Prestate cancer Improved survival (calciterol + chemo vs. chemo alone) but not the reduced PSA (primary outcome)

Beer 2007 Prostate cancer Trial stopped by safety monitoring committee.

Attia 2008 Prostate cancer (Doxecalceferol + chemo) used, no clinical benefit.

Chadha 2010 Prostate cancer High dose IV calciterol + dexa., did not decrease PSA.

• Studies targeting cancer outcomes :

- J.M. Lappe, D. Travers-Gustafson, K.M. Davies, R.R. Recker, R.P. Heaney, Am. J. Clin. 652 Nutr. 85 (2007) 1586–1591. -R.T. Chlebowski, K.C. Johnson, C. Kooperberg, M. Pettinger, J. Wactawski- Wende, T. Rohan, J. Rossouw, D. Lane, M.J. O'Sullivan, S. Yasmeen, R.A. Hiatt, J.M.655 Shikany, M. Vitolins, J. Khandekar, F.A. Hubbell, J. Natl. Cancer Inst. 100 (2008) 656 1581–1591.- J. Wactawski-Wende, J.M. Kotchen, G.L. Anderson, A.R. Assaf, R.L. Brunner, M.J. O'Sullivan, K.L. Margolis, J.K. Ockene, L. Phillips, L. Pottern, R.L. Prentice, J. Robbins, T.E. Rohan, G.E. Sarto, S. Sharma, M.L. Stefanick, L. Van Horn, R.B. Wallace, E. Whitlock, T. Bassford, S.A. Beresford, H.R. Black, D.E. Bonds, R.G. Brzyski, B. Caan, R.T. Chlebowski, B. Cochrane, C. Garland, M. Gass, J. Hays, G. Heiss, S.L. Hendrix, B.V. Howard, J. Hsia, F.A. Hubbell, R.D. Jackson, K.C. Johnson, H. Judd, C.L. Kooperberg, L.H. Kuller, A.Z. LaCroix, D.S. Lane, R.D. Langer, N.L. 664 Lasser, C.E. Lewis, M.C. Limacher, J.E. Manson, N. Engl. J. Med. 354 (2006) 665 684–696.- E.L. Ding, S. Mehta, W.W. Fawzi, E.L. Giovannucci, Int. J. Cancer 122 (2008) 1690–1694. -D.P. Trivedi, R. Doll, K.T. Khaw, BMJ 326 (2003) 469.

Author Year Cancer Main finding

Lappe 2007 All types High dose vit. D . Reduction in all cancer types ( breast, colon, lung, hemopoitic malignancies)

R.T. chlebowski

2008 Breast cancer Low-dose vit. D.No difference in breast cancer.

D.P. Trivedi 2003 all cancers High-dose vit. D. No difference.

• Conclusion..

• Thank you.

• Conclusion..