An introduction to cancerPrevention

Meta-analysis of all available studies of serum 25(OH)D level with respect to a particular cancer is used to determine the dose-response relation for cancer incidence.

There are two observational approaches for ascertaining the role of vitamin D in the risk of cancer: case-control and nested case-control studies.

The primary difference between the two approaches is the time between serum 25(OH)D level determination and incidence of cancer: the lag time is essential zero for case-control studies but anywhere from several years to 28 years for nested case-control studies.

Only case-control studies consistently find inverse correlations between serum 25(OH)D level and cancer incidence for breast cancer1. Nested case-control studies generally do not find inverse correlations23.

However, those from Harvard have45 as do those for colorectal cancer6. In these studies, the lag between serum 25(OH)D level determination and cancer incidence was 2-4 years. The reason why short lag times may be important may be that once tumors reach a diameter of 1-3 mm, they generate a vascular system (angiogenesis) to obtain nutrients at a faster rate7. After that, tumors grow very rapidly8.

Meta-analyses for an increase in serum 25(OH)D from 20 ng/ml to 40 ng/ml show significantly reduced risk of about 35% for breast cancer9101 and colorectal cancer9106.

Results of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) were recently published2. The VDPP was comprised of ten cohort studies, seven from the United States, two from China, and one from Finland. There were anywhere from 516 to 1353 cases for each type of cancer. Those in the cohorts were observed for a mean follow up time of about ten years. Contrary to the results from numerous ecological studies, no beneficial effect of serum 25(OH)D level was found for the seven cancers studied: endometrial, esophageal, gastric, kidney, ovarian, and pancreatic cancer and NHL; in fact there was an increased odds ratio for pancreatic cancer at the highest serum 25(OH)D level. While it is difficult to determine why the results of the VDPP differ from both ecological studies for these types of cancer and from breast and colorectal cancer observational studies, it may be possible that the long follow up time rendered the serum 25(OH)D level from the time of enrollment inaccurate. For example, a study of Finnish smokers found lymphoma cases diagnosed less than 7 years from the baseline showed an inverse association (OR for highest vs. lowest tertile = 0.43; 95% CI: 0.23, 0.83; p for trend = 0.01), but not later diagnoses (OR = 1.52; 95% CI: 0.82, 2.80; p for trend = 0.17)3

After the VDPP papers were published, an observational study from Finland found having serum 25(OH)D >57.8 nmol/L vs <57.8 nmol/ excluding cases who donated serum samples within 1–3 years of cancer diagnosis gave an adjusted OR 0.49 (0.24–1.01) for ovarian cancer11

There are also a few observational studies of beneficial effects for oral intake of vitamin D for the rarer cancers: endometrial12, esophageal13, kidney14, ovarian15, pancreatic cancer165 and NHL17

There has been one successful RCT of vitamin D supplementation with respect to cancer incidence. In a study involving post menopausal women living in Nebraska, those taking 1100 IU/day of vitamin D3 and 1450 mg/day of calcium had a 77% reduction in all-cancer incidence between the ends of the first and fourth years, while those taking only the calcium had a 40% risk reduction18. Calcium seems to reduce the risk of cancer independently from vitamin D19. Those taking vitamin D supplements in the Lappe et al. study increased their serum 25(OH)D levels from 29 ng/mL to 39 ng/mL.

An earlier RCT in England involving 100 000 IU oral vitamin D3 supplementation or matching placebo every four months (equivalent to 833 IU/day) over five years found an age-adjusted relative risk for cancer mortality of 0.93 (95% CI, 0.64-1.34) for males and 0.53 (0.21-1.33) for females20

Page last edited: 04 May 2011

References

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. Skinner HG, Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Vitamin D intake and the risk of pancreatic cancer in two cohort studies. Cancer Epidemiol Biomarkers Prevention. 2006 Sept; 15 (9): 1688-1695.
  6. 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.
  7. Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology. 2005; 69 (Supp 3): 4-10.
  8. Weedon-Fekjaer H, Lindqvist BH, Vatten LJ, Aalen OO, Tretli S. Breast cancer tumor growth estimated through mammography screening data. Breast Cancer Res. 2008; 10 (3):
  9. 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;
  10. 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;
  11. Toriola, A. T. Surcel, H. M. Calypse, A. Grankvist, K. Luostarinen, T. Lukanova, A. Pukkala, E. Lehtinen, M. Independent and joint effects of serum 25-hydroxyvitamin D and calcium on ovarian cancer risk: A prospective nested case-control study. Eur J Cancer. 2010 Jun 18;
  12. Salazar-Martinez, E. Lazcano-Ponce, E. Sanchez-Zamorano, L. M. Gonzalez-Lira, G. Escudero, D. E. Los Rios P. Hernandez-Avila, M. Dietary factors and endometrial cancer risk. Results of a case-control study in Mexico. Int J Gynecol Cancer. 2005 Sep-Oct; 15 (5): 938-45.
  13. Launoy, G. Milan, C. Day, N. E. Pienkowski, M. P. Gignoux, M. Faivre, J. Diet and squamous-cell cancer of the oesophagus: a French multicentre case-control study. Int J Cancer. 1998 Mar 30; 76 (1): 7-12.
  14. Bosetti, C. Scotti, L. Maso, L. D. Talamini, R. Montella, M. Negri, E. Ramazzotti, V. Franceschi, S. La Vecchia, C. Micronutrients and the risk of renal cell cancer: a case-control study from Italy. Int J Cancer. 2007 Feb 15; 120 (4): 892-6.
  15. Salazar-Martinez, E. Lazcano-Ponce, E. C. Gonzalez Lira-Lira, G. Escudero-De los Rios, P. Hernandez-Avila, M. Nutritional determinants of epithelial ovarian cancer risk: a case-control study in Mexico. Oncology. 2002; 63 (2): 151-7.
  16. 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.
  17. Polesel, J. Talamini, R. Montella, M. Parpinel, M. Dal Maso, L. Crispo, A. Crovatto, M. Spina, M. La Vecchia, C. Franceschi, S. Linoleic acid, vitamin D and other nutrient intakes in the risk of non-Hodgkin lymphoma: an Italian case-control study. Ann Oncol. 2006 Apr; 17 (4): 713-8.
  18. Lappe, J. M. Travers-Gustafson, D. Davies, K. M. Recker, R. R. Heaney, R. P. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007 Jun; 85 (6): 1586-91.
  19. Peterlik, M. Grant, W. B. Cross, H. S. Calcium, vitamin D and cancer. Anticancer Res. 2009 Sep; 29 (9): 3687-98.
  20. Trivedi, D. P. Doll, R. Khaw, K. T. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003 Mar 1; 326 (7387): 469.