Original Article

Relationship of Vitamin D Monitoring and Status to Bladder Cancer Survival in Veterans

Authors: Alan N. Peiris, MD, Beth A. Bailey, PhD, Todd Manning, BA

Abstract

Objectives: Veterans of the armed forces, like most population groups, have a high prevalence of vitamin D deficiency, which may be associated with adverse outcomes in several types of cancer. Ultraviolet irradiation is inversely linked with the risk of bladder cancer, presumably through enhanced vitamin D synthesis. We hypothesized that variations in vitamin D status and monitoring predict adverse outcomes in bladder cancer among veterans.


Methods: A retrospective analysis of data in the Veterans Integrated Service Network-9 (southeastern United States) was performed for patients diagnosed between October 1, 1999 and February 29, 2008. Age, tobacco exposure, body mass index, and latitude and seasonality of sampling were included as variables in addition to serum vitamin 25(OH)D levels.


Results: Monitoring of vitamin D and vitamin D levels and status were closely linked to survival in bladder cancer. Both the chances of survival and longevity improved with enhanced vitamin D status and monitoring. Veterans with bladder cancer had better outcomes if the initial vitamin D level was higher and had more monitoring of the vitamin. Initial vitamin D levels were more strongly related to outcomes than follow-up levels. The link between vitamin D and outcomes remained after adjusting for background variables such as age, body mass index, latitude, seasonality, and tobacco exposure.


Conclusions: Findings suggest that adequate vitamin D levels early in the course of the disease provide the best opportunity to improve outcomes. Ensuring that veterans with bladder cancer have adequate vitamin D reserves with appropriate monitoring may play a role in improving outcomes in bladder cancer.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 2008; 87: 1080S–1086S.
 
2. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 2007; 167: 1730–1737.
 
3. Peiris AN, Bailey BA, Manning T, et al. Are 25-hydroxyvitamin D levels adequately monitored following evidence of vitamin D insufficiency in veterans? Mil Med 2010; 175: 453–456.
 
4. Bailey BA, Manning T, Peiris AN. Vitamin D testing patterns among six Veterans Medical Centers in the southeastern United States: links with medical costs. Mil Med 2012; 177: 70–76.
 
5. Ooi LL, Zheng Y, Zhou H, et al. Vitamin D deficiency promotes growth of MCF-7 human breast cancer in a rodent model of osteosclerotic bone metastasis. Bone 2010; 47: 795–803.
 
6. Avritscher EB, Cooksley CD, Grossman HB, et al. Clinical model of lifetime cost of treating bladder cancer and associated complications. Urology 2006; 68: 549–553.
 
7. Mohr SB, Garland CF, Gorham ED, et al. Ultraviolet B irradiance and incidence rates of bladder cancer in 174 countries. Am J Prev Med 2010; 38: 296–302.
 
8. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266–281.
 
9. Peiris AN, Bailey BA, Guha BN, et al. Can a model predictive of vitamin D status be developed from common laboratory tests and demographic parameters? South Med J 2011; 104: 636–639.
 
10. Moan J, Dahlback A, Lagunova Z, et al. Solar radiation, vitamin D and cancer incidence and mortality in Norway. Anticancer Res 2009; 29: 3501–3509.
 
11. Grant WB. Ecological studies of the UVB-vitamin D-cancer hypothesis. Anticancer Res 2012; 32: 223–236.
 
12. Sahin MO, Canda AE, Yorukoglu K, et al. 1,25 Dihydroxyvitamin D(3) receptor expression in superficial transitional cell carcinoma of the bladder: a possible prognostic factor? Eur Urol 2005; 47: 52–57.
 
13. Mondul AM, Weinstein SJ, Mannisto S, et al. Serum vitamin D and risk of bladder cancer. Cancer Res 2010; 70: 9218–9223.
 
14. Neuhouser ML, Wassertheil-Smoller S, Thomson C, et al. Multivitamin use and risk of cancer and cardiovascular disease in the Women’s Health Initiative cohorts. Arch Intern Med 2009; 169: 294–304.
 
15. Grant WB, Peiris AN. Differences in vitamin D status may account for unexplained disparities in cancer survival rates between African and white Americans. Dermato-endocrinology 2012; 4: 85–94.
 
16. Mittal RD, Manchanda PK, Bhat S, et al. Association of vitamin-D receptor (Fok-I) gene polymorphism with bladder cancer in an Indian population. BJU Int 2007; 99: 933–937.
 
17. Opolski A, Wietrzyk J, Chrobak A, et al. Antiproliferative activity in vitro of side-chain analogues of calcitriol against various human normal and cancer cell lines. Anticancer Res 1999; 19: 5217–5222.
 
18. Ma Y, Yu WD, Trump DL, et al. 1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models. Cancer 2010; 116: 3294–3303.
 
19. Konety BR, Lavelle JP, Pirtskalaishvili G, et al. Effects of vitamin D (calcitriol) on transitional cell carcinoma of the bladder in vitro and in vivo. J Urol 2001; 165: 253–258.
 
20. Shokravi MT, Marcus DM, Alroy J, et al. Vitamin D inhibits angiogenesis in transgenic murine retinoblastoma. Invest Ophthalmol Vis Sci 1995; 36: 83–87.
 
21. Zhuravel E, Efanova O, Shestakova T, et al. Administration of vitamin D3 improves antimetastatic efficacy of cancer vaccine therapy of Lewis lung carcinoma. Exp Oncol 2010; 32: 33–39.
 
22. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 1911–1930.