Vitamin D and Pancreatic Cancer

Pancreatic cancer

Pancreatic cancer is cancer of the pancreas, the organ that produces insulin. Approximately 44,000 people in the United States are diagnosed with cancer of the pancreas each year. It is one of the most deadly cancers and causes as many as 37,000 deaths annually. The disease is often diagnosed at an advanced stage. By then, treatment may not be effective.

Risk factors

Some of the more important risk factors for this cancer include:

• Diet high in simple carbohydrates and meat: Simple carbohydrates (white rice, baked goods) are foods that turn into sugar quickly. Sugar, meat, and fat contribute to the metabolic syndrome. This is characterized by extra abdominal fat and insulin resistance. This syndrome increases the risk of many diseases.
• Obesity: This health threat may also contribute to the metabolic syndrome.
• Smoking: Smoking contributes to the risk of pancreatic cancer.

A diet high in vegetables is associated with a reduced risk of pancreatic cancer

Sunlight exposure and pancreatic cancer risk

Several studies have researched solar ultraviolet-B (UVB) light, vitamin D, and pancreatic cancer. The studies concluded that:

• There was a lower incidence and death rate from pancreatic cancer in people exposed to higher levels of solar UVB light. These studies appear to be reliable and accurate. They researched the effects of UVB light during an entire lifetime. There have been similar results in Japan and the United States.
• People who live in warm, sunny climates produce adequate levels of vitamin D. They have a higher risk of nonmelanoma skin cancer. But they have a lower risk of pancreatic cancer.

Vitamin D and pancreatic cancer

Vitamin D levels

Two Harvard studies found a correlation between vitamin D and pancreatic cancer:

• One study compared people taking 150 vs 600 international units (IU) (3.8 vs 15 mcg)  vitamin D per day. There was a 40% lower cancer risk in people who took more vitamin D.
• The other study found a 35% lower risk for those with higher vitamin D blood levels.

Other studies using a single value of vitamin D blood level did not find beneficial effects of vitamin D. However, the long follow-up times after blood level measurement greatly reduces the value of the study.

How vitamin D works

Vitamin D has been shown to block the growth of cancer tumors. Vitamin D is processed by the liver. The body then produces calcitriol, an active form of vitamin D. Calcitriol provides numerous benefits against cancer. This form of vitamin D encourages cells to either adapt to their organ or commit apoptosis (cell suicide). Calcitriol also limits blood supply to the tumor and reduces the spread of cancer.

Prevention

High levels of vitamin D are associated with a lower risk of pancreatic cancer based on both observational studies of individuals and geographic studies of populations. Based on studies of breast, colon, and rectal cancer, vitamin D levels above 40 ng/mL (100 nmol/L) reduce the risk of cancer. Thus, maintaining vitamin D blood levels above 40 ng/mL may reduce the risk of pancreatic cancer. Taking 1000–4000 international units (IU) (25–100 mcg)/day of vitamin D may be associated with reduced pancreatic cancer risk.

Vitamin D and calcium

Studies have shown that taking both vitamin D and calcium provides additional cancer protection against many types of cancer. Calcium intake of more than 1000 mg/day from either diet or supplements is recommended. Patients in one study took daily doses of 1100 IU (27.5 mcg) vitamin D and 1450 mg calcium. These patients had a 77% reduction in the incidence of all types of cancer between the ends of the first and fourth years of the study.

Treatment

People with higher vitamin D levels at time of cancer diagnosis have a higher survival rate. This is true for people with many types of cancer. Studies suggest that increasing vitamin D levels after cancer diagnosis would improve chances of survival. Some treatment centers are now giving at least 5000 IU (125 mcg)/day vitamin D to patients with cancer. Outcome results have yet to be published.

Acknowledgements

William B. Grant, Ph.D.
Sunlight, Nutrition, and Health Research Center (SUNARC)
P.O. Box 641603
San Francisco, CA 94164-1603, USA
www.sunarc.org
wbgrant@infionline.net

The summary was reviewed by:

• Albert Lowenfels, <Al_Lowenfel@nymc.edu>

Complete bibliography of research used in this summary

The research we have cited in our summary is listed below, with links to PubMed abstracts and full-text for those who wish to explore further.

References

1. Arnold LD, Patel AV, Yan Y, et al Are racial disparities in pancreatic cancer explained by smoking and overweight/obesity?. Cancer Epidemiol Biomarkers Prev. 2009; 18 (9): 2397–405.
2. Bao, Y. Ng, K. Wolpin, B. M. Michaud, D. S. Giovannucci, E. Fuchs, C. S. Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies. Br J Cancer. 2010 Apr 27; 102 (9): 1422-7.
3. Barreto, S. G. Ramadwar, M. R. Shukla, P. J. Shrikhande, S. V. Vitamin D3 in operable periampullary and pancreatic cancer: perioperative outcomes in a pilot study assessing safety. Pancreas. 2008 Apr; 36 (3): 315-7.
4. Boscoe, F. P. Schymura, M. J. Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993-2002. BMC Cancer. 2006; 6264.
5. Bulathsinghala, P. Syrigos, K. N. Saif, M. W. Role of vitamin d in the prevention of pancreatic cancer. Journal of nutrition and metabolism. 2010; 2010721365.
6. Chiang, K. C. Chen, T. C. Vitamin D for the prevention and treatment of pancreatic cancer. World J Gastroenterol. 2009 Jul 21; 15 (27): 3349-54.
7. Gandini, S. Boniol, M. Haukka, J. Byrnes, G. Cox, B. Sneyd, M. J. Mullie, P. Autier, P. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2010 May 6;
8. Ginde, A.A. et al. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009, Mar; 169 (6): 626-32.
9. Giovannucci, E. Liu, Y. Rimm, E. B. Hollis, B. W. Fuchs, C. S. Stampfer, M. J. Willett, W. C. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006 Apr 5; 98 (7): 451-9.
10. Grant, W. B. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer. 2002 Mar 15; 94 (6): 1867-75.
11. Grant, W. B. Ecologic studies of solar UV-B radiation and cancer mortality rates. Recent Results Cancer Res. 2003; 164371-7.
12. Grant, W. B. An ecologic study of cancer mortality rates in Spain with respect to indices of solar UVB irradiance and smoking. Int J Cancer. 2007 Mar 1; 120 (5): 1123-8.
13. Grant, W. B. The effect of solar UVB doses and vitamin D production, skin cancer action spectra, and smoking in explaining links between skin cancers and solid tumours. Eur J Cancer. 2008 Jan; 44 (1): 12-5.
14. Grant, W. B. How strong is the evidence that solar ultraviolet B and vitamin D reduce the risk of cancer?: An examination using Hill’s criteria for causality. Dermatoendocrinol. 2009 Jan; 1 (1): 17-24.
15. Grant, W. B. Re: “Overview of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers”. Am J Epidemiol. 2010 Sep 8;
16. Grant, W. B. Relation between prediagnostic serum 25-hydroxyvitamin D level and incidence of breast, colorectal, and other cancers. J Photochem Photobiol B. 2010 May 12;
17. Grant, W. B. Garland, C. F. The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Anticancer Res. 2006 Jul-Aug; 26 (4A): 2687-99.
18. Grant, W. B. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level; implications for meta-analyses and setting vitamin D guidelines. Dermato-endocrinology. 2011; 3 (3):
19. Helzlsouer, K. J. Overview of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. 2010 Jul 1; 172 (1): 4-9.
20. Hypponen, E. Power, C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007 Mar; 85 (3): 860-8.
21. Jorde, R. Saleh, F. Figenschau, Y. Kamycheva, E. Haug, E. Sundsfjord, J. Serum parathyroid hormone (PTH) levels in smokers and non-smokers. The fifth Tromsø study. Eur J Endocrinol. 2005 Jan.; 52 (1): 39-45.
22. Jupp, J. Fine, D. Johnson, C. D. The epidemiology and socioeconomic impact of chronic pancreatitis. Best Pract Res Clin Gastroenterol. 2010 Jun; 24 (3): 219-31.
23. Kato, I. Tajima, K. Kuroishi, T. Tominaga, S. Latitude and pancreatic cancer. Jpn J Clin Oncol. 1985 Jun; 15 (2): 403-13.
24. Kawa, S. Nikaido, T. Aoki, Y. Zhai, Y. Kumagai, T. Furihata, K. Fujii, S. Kiyosawa, K. Vitamin D analogues up-regulate p21 and p27 during growth inhibition of pancreatic cancer cell lines. Br J Cancer. 1997; 76 (7): 884-9.
25. Kinoshita, S. Wagatsuma, Y. Okada, M. Geographical distribution for malignant neoplasm of the pancreas in relation to selected climatic factors in Japan. Int J Health Geogr. 2007; 634.
26. Krejs, G. J. Pancreatic cancer: epidemiology and risk factors. Dig Dis. 2010; 28 (2): 355-8.
27. Leffell, B. et al. Sunlight and skin cancer. Sci Am. 1996; 275 (1): 52-3, 56-9.
28. Lim, U. Freedman, D. M. Hollis, B. W. Horst, R. L. Purdue, M. P. Chatterjee, N. Weinstein, S. J. Morton, L. M. Schatzkin, A. Virtamo, J. Linet, M. S. Hartge, P. Albanes, D. A prospective investigation of serum 25-hydroxyvitamin D and risk of lymphoid cancers. Int J Cancer. 2009 Feb 15; 124 (4): 979-86.
29. Michaelsson, K. Lithell, H. Vessby, B. Melhus, H. Serum retinol levels and the risk of fracture. N Engl J Med. 2003 Jan 23; 348 (4): 287-94.
30. Mizoue, T. Ecological study of solar radiation and cancer mortality in Japan. Health Phys. 2004 Nov; 87 (5): 532-8.
31. Mohr, S. B. Garland, C. F. Gorham, E. D. Grant, W. B. Garland, F. C. Ultraviolet B irradiance and vitamin D status are inversely associated with incidence rates of pancreatic cancer worldwide. Pancreas. 2010 Jul; 39 (5): 669-74.
32. Neale, R. E. Youlden, D. R. Krnjacki, L. Kimlin, M. G. van der Pols, J. C. Latitude variation in pancreatic cancer mortality in Australia. Pancreas. 2009 May; 38 (4): 387-90.
33. Oh, E. Y. Ansell, C. Nawaz, H. Yang, C. H. Wood, P. A. Hrushesky, W. J. Global breast cancer seasonality. Breast Cancer Res Treat. 2010 Aug; 123 (1): 233-43.
34. Peterlik, M. Grant, W. B. Cross, H. S. Calcium, vitamin D and cancer. Anticancer Res. 2009 Sep; 29 (9): 3687-98.
35. Pettersson, F. Colston, K. W. Dalgleish, A. G. Differential and antagonistic effects of 9-cis-retinoic acid and vitamin D analogues on pancreatic cancer cells in vitro. Br J Cancer. 2000 Jul; 83 (2): 239-45.
36. Raimondi, S. Lowenfels, A. B. Morselli-Labate, A. M. Maisonneuve, P. Pezzilli, R. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol. 2010 Jun; 24 (3): 349-58.
37. Schwartz, G. G. Eads, D. Rao, A. Cramer, S. D. Willingham, M. C. Chen, T. C. Jamieson, D. P. Wang, L. Burnstein, K. L. Holick, M. F. Koumenis, C. Pancreatic cancer cells express 25-hydroxyvitamin D-1 alpha-hydroxylase and their proliferation is inhibited by the prohormone 25-hydroxyvitamin D3. Carcinogenesis. 2004 Jun; 25 (6): 1015-26.
38. Skinner, H. G. Vitamin D for the treatment and prevention of pancreatic cancer. Cancer Biol Ther. 2008 Mar; 7 (3): 437-9.
39. Skinner, H. G. Michaud, D. S. Giovannucci, E. Willett, W. C. Colditz, G. A. Fuchs, C. S. Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiol Biomarkers Prev. 2006 Sep; 15 (9): 1688-95.
40. Stolzenberg-Solomon, R. Z. Vitamin D and pancreatic cancer. Ann Epidemiol. 2009 Feb; 19 (2): 89-95.
41. Stolzenberg-Solomon, R. Z. Hayes, R. B. Horst, R. L. Anderson, K. E. Hollis, B. W. Silverman, D. T. Serum vitamin D and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian screening trial. Cancer Res. 2009 Feb 15; 69 (4): 1439-47.
42. Stolzenberg-Solomon, R. Z. Vieth, R. Azad, A. Pietinen, P. Taylor, P. R. Virtamo, J. Albanes, D. A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Cancer Res. 2006 Oct 15; 66 (20): 10213-9.
43. Tuohimaa, P. Pukkala, E. Scelo, G. Olsen, J. H. Brewster, D. H. Hemminki, K. Tracey, E. Weiderpass, E. Kliewer, E. V. Pompe-Kirn, V. McBride, M. L. Martos, C. Chia, K. S. Tonita, J. M. Jonasson, J. G. Boffetta, P. Brennan, P. Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: vitamin D as a possible explanation. Eur J Cancer. 2007 Jul; 43 (11): 1701-12.
44. Yin, L. Grandi, N. Raum, E. Haug, U. Arndt, V. Brenner, H. Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk. Aliment Pharmacol Ther. 2009 Jul 1; 30 (2): 113-25.
45. Yin, L. Grandi, N. Raum, E. Haug, U. Arndt, V. Brenner, H. Meta-analysis: serum vitamin D and breast cancer risk. Eur J Cancer. 2010 Aug; 46 (12): 2196-205.
46. Zugmaier, G. Jager, R. Grage, B. Gottardis, M. M. Havemann, K. Knabbe, C. Growth-inhibitory effects of vitamin D analogues and retinoids on human pancreatic cancer cells. Br J Cancer. 1996 Jun; 73 (11): 1341-6.