The role for Vitamin D and its active metabolite, 1,25-dihydroxy-vitamin D in slowing cancer progression has been demonstrated in numerous preclinical studies; however, results from human studies has been inconclusive [1]. Current evidence from in vitro [2-4] and in vivo [5] studies suggest that a possible mechanism by which Vitamin D decreases proliferation and stimulates apoptosis of breast tumours is by antagonizing the effects of IGF-I and by stimulating the expression of IGFBP-3. It was also shown that IGFBP-3 mediates Vitamin D induced growth inhibition of prostate cancer cells via p21/WAF1 [6]. Given the interest in the potential role of Vitamin D in inhibiting cancer progression, further research is needed to investigate the mechanisms underlying these associations.
This proposal is for a Recall by Genotype study to recall individuals stratified by genetic risk scores for Vitamin D (based on genetic variants that affect Vitamin D synthesis, metabolism and transport) to enable detailed and precise phenotyping

References:
1.Feldman, D., A.V. Krishnan, S. Swami, E. Giovannucci and B.J. Feldman, The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer, 2014. 14(5): p. 342-57.
2. Xie, S.P., S.Y. James and K.W. Colston, Vitamin D derivatives inhibit the mitogenic effects of IGF-I on MCF-7 human breast cancer cells. J Endocrinol, 1997. 154(3): p. 495-504.
3. Colston, K.W., C.M. Perks, S.P. Xie and J.M. Holly, Growth inhibition of both MCF-7 and Hs578T human breast cancer cell lines by vitamin D analogues is associated with increased expression of insulin-like growth factor binding protein-3. J Mol Endocrinol, 1998. 20(1): p. 157-62.
4. Xie, S.P., G. Pirianov and K.W. Colston, Vitamin D analogues suppress IGF-I signalling and promote apoptosis in breast cancer cells. Eur J Cancer, 1999. 35(12): p. 1717-23.
5. Lee, H.J., S. Paul, N. Atalla, P.E. Thomas, X. Lin, I. Yang, B. Buckley, G. Lu, X. Zheng, Y.R. Lou, A.H. Conney, H. Maehr, L. Adorini, M. Uskokovic and N. Suh, Gemini vitamin D analogues inhibit estrogen receptor-positive and estrogen receptor-negative mammary tumorigenesis without hypercalcemic toxicity. Cancer Prev Res (Phila), 2008. 1(6): p. 476-84.
6. Boyle, B.J., X.Y. Zhao, P. Cohen and D. Feldman, Insulin-like growth factor binding protein-3 mediates 1 alpha,25-dihydroxyvitamin d(3) growth inhibition in the LNCaP prostate cancer cell line through p21/WAF1. J Urol, 2001. 165(4): p. 1319-24.