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Serum vitamin D concentration and prostate cancer risk: a nested case-control study. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, Horst RL, Hollis BW, Huang WY, Shikany JM, Hayes RB; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Project Team. J Natl Cancer Inst. 2008 Jun 4;100(11):796-804. Epub 2008 May 27. PMID: 18505967 doi:10.1093/jnci/djn152 CONCLUSION: The findings of this large prospective study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer; indeed, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease. In summary, results from this large prospective study of men who underwent standardized prostate cancer screening in the context of a screening trial do not support the hypothesis that higher serum vitamin D status is associated with decreased risk of prostate cancer. The study showed no association of vitamin D level with nonaggressive disease; however, it raises the possibility that higher vitamin D level may be associated with increased risks for aggressive disease, although a clear monotonic dose-response relationship was lacking. Along with recent reports of adverse associations for higher vitamin D status and risk of pancreatic (32) and esophageal (33,34) cancer, caution should be taken in recommending high doses of vitamin D or sunlight exposure to the general public for prostate cancer prevention. Future analyses are warranted to confirm these results and to further clarify the effects of vitamin D on aggressive prostate cancer.

Vitamin D, aging, and cancer. Tuohimaa P. Nutr Rev. 2008 Oct;66(10 Suppl 2):S147-52. Review. PMID: 18844842 DOI: 10.1111/j.1753-4887.2008.00095.x Deficiency of the prohormone calcidiol (25OH vitamin D3) seems to be associated with several aging-related chronic diseases including cancer. Our results suggest that calcidiol is mainly responsible for differentiation homeostasis, whereas calcitriol might be more involved in calcium homeostasis. Therefore, an imbalance of calcidiol rather than calcitriol is a risk factor for cancer and chronic diseases. Calcidiol insufficiency, as well as insufficient solar exposure, is associated with increased risk of several solid cancers. Both a vitamin D3 deficiency and a high concentration of calcidiol may increase cancer risk. Similarly, aging phenomena show a U-shaped association with vitamin D bioactivity. Therefore, the chronic diseases and cancers related to aging might be prevented by an optimal concentration of serum calcidiol, which remains to be determined.

Sunlight, vitamin D and the prevention of cancer: a systematic review of epidemiological studies. Rhee HV, Coebergh JW, Vries ED. Eur J Cancer Prev. 2009 Aug 26. [Epub ahead of print] PMID: 19730382 We, therefore, conclude that there is accumulating evidence for sunlight as a protective factor for several types of cancer. The same conclusion can be made concerning high vitamin D levels and the risk of colorectal cancer. This evidence, however, is not conclusive, because the number of (good quality) studies is still limited and publication biases cannot be excluded. The discrepancies between the epidemiological evidence for a possible preventive effect of sunlight and vitamin D and the question of how to apply the findings on the beneficial effects of sunlight to (public) health recommendations are discussed.

"Under year round UV exposure conditions (low latitudes, broken line, "High UV") there is no association between 25(OH)D and either prostate or pancreatic cancer. At high latitudes (Solid line, "Low UV") there is a positive association between blood levels of 25(OH)D and these cancers. The average year round levels of 25(OH)D actually tend to be higher in northern latitudes, higher than those where there is year-round solar UVB. Vieth explains that we know almost nothing about the enzymes controlling tissue 1,25(OH)2D levels and much of his discussion is extrapolated from renal enzyme activity."

Inverse association between serum 25(OH) vitamin D levels and non-melanoma skin cancer in elderly men. Tang JY, Parimi N, Wu A, John Boscardin W, Shikany JM, Chren MM, Cummings SR, Epstein EH Jr, Bauer DC; for the Osteoporotic Fractures in Men (MrOS) Study Group. Cancer Causes Control. 2009 Nov 18. [Epub ahead of print] PMID: 19921445 Our results suggest that a diagnosis of NMSC is not a surrogate for adequate 25(OH)D levels or increased UV exposure, and high 25(OH)D levels may be associated with a reduced risk of NMSC.

Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Tuohimaa P, Tenkanen L, Ahonen M, Lumme S, Jellum E, Hallmans G, Stattin P, Harvei S, Hakulinen T, Luostarinen T, Dillner J, Lehtinen M, Hakama M. Int J Cancer. 2004 Jan 1;108(1):104-8. PMID: 14618623 DOI: 10.1002/ijc.11375

High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy. Crew KD, Shane E, Cremers S, McMahon DJ, Irani D, Hershman DL. J Clin Oncol. 2009 May 1;27(13):2151-6. Epub 2009 Apr 6. PMID: 19349547 DOI: 10.1200/JCO.2008.19.6162 Conclusion Vitamin D deficiency is highly prevalent in women with breast cancer. The current recommended dietary allowance of vitamin D is too low to increase serum 25-OHD greater than 30 ng/mL. Optimal dosing for bone health and, possibly, improved survival has yet to be determined.

Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk. Mikhak B, Hunter DJ, Spiegelman D, Platz EA, Hollis BW, Giovannucci E. Prostate. 2007 Jun 15;67(9):911-23. PMID: 17440943 DOI: 10.1002/pros.20570 RESULTS No association was found between these SNPs or their associated haplotypes and all PC subtypes except that haplotype 2 (A-f-b) with Cdx2 A, Fok1 f, and Bsm1 b alleles and haplotype 3 (A-F-B) with Cdx2 A, Fok1 F and Bsm1 B alleles compared to the most common haplotype (A-F-b), were associated with reduced risk of aggressive PC (high stage or Gleason sum 7; P = 0.02), both with two alleles suspected of being low risk. Carriers of the variant Cdx2 A allele who were deficient in plasma 25-hydroxyvitamin D (15 ng/ml) compared to non-carriers with normal 25-hydroxyvitamin D, had a lower risk of total and poorly differentiated PCs (Gleason sum 7) (P for interaction = 0.02 and 0.04, respectively). Plasma 1,25-dihydroxyvitamin D deficiency (26 pg/ml) was associated with a threefold risk of poorly differentiated PC (P for interaction = 0.01) when comparing carriers of the Cdx2 A allele to non-carriers with normal 1,25-dihydroxyvitamin D. CONCLUSION In this population of men, none of the VDR polymorphisms studied was associated with susceptibility to PC. Carriers of the variant Cdx2 A allele with low plasma 25-hydroxyvitamin D may experience a reduction in risk of total and poorly differentiated prostate cancers compared to non-carriers with adequate 25-hydroxyvitamin D.

Vitamin D association with estradiol and progesterone in young women. Knight JA, Wong J, Blackmore KM, Raboud JM, Vieth R. Cancer Causes Control. 2009 Nov 15. [Epub ahead of print] PMID: 19916051 Conclusions Higher levels of vitamin D may reduce progesterone and estradiol, providing a potential mechanism for reduction in breast cancer risk from increased vitamin D exposure in young women

"ScienceDaily (Oct. 8, 2009) - Women with breast cancer should be given high doses of vitamin D because a majority of them are likely to have low levels of vitamin D, which could contribute to decreased bone mass and greater risk of fractures, according to scientists at the University of Rochester Medical Center." Scientists funded by the NCI analyzed vitamin D levels in each woman, and the average level was 27 nanograms per milliliter; more than two-thirds of the women had vitamin deficiency. Weekly supplementation with high doses of vitamin D -- 50,000 international units or more -- improved the levels, according to Peppone's study. The U.S. Institute of Medicine suggests that blood levels nearing 32 nanograms per milliliter are adequate.

Evidence from clinical trials shows, with a wide margin of confidence, that a prolonged intake of 10,000IU/d of vitamin D3 poses no risk of adverse effects for adults, even if this is added to a rather high physiologic background level of vitamin D. Vitamin D and cancer mini-symposium: the risk of additional vitamin D. Vieth R.\nAnn Epidemiol. 2009 Jul;19(7):441-5. Epub 2009 Apr 11. PMID: 19364661 doi:10.1016/j.annepidem.2009.01.009