Vitamin D and Ovarian Cancer

Ovarian cancer

Ovarian cancer is cancer that starts in the ovaries. As it has few symptoms at first, it is often diagnosed at more advanced stages. Each year, ovarian cancer affects approximately 22,000 women in the United States. It is one of the most deadly cancers and kills about 15,000 annually.

Risk factors

Ovarian cancer may be affected by a diet high in animal products. These foods have a lot of protein and fat, which increase the amount of growth factor. Growth factors help the body grow. They also help tumors grow. Dairy products such as milk may also be associated with increased risk of ovarian cancer. Studies have shown that the risk of ovarian cancer may be lowered by:

• Physical activity
• Oral contraceptive use

Sunlight exposure and ovarian cancer risk

Ovarian cancer is one of the top 19 cancers sensitive to vitamin D. Several studies show that mortality rates for this cancer are lower in areas with more solar ultraviolet-B (UVB) light. This is similar to findings of other cancers including breast cancer. A study from Spain on women living in different provinces and their sun exposure, especially in summer found women with more sun exposure had higher death rates from non-melanoma skin cancer. Interestingly, these women also had lower death rates from ovarian cancer.

Vitamin D and ovarian cancer

Vitamin D levels

A study found that U.S. women with ovarian cancer were four times more likely to have low vitamin D blood levels than women without ovarian cancer. This study compared vitamin D levels greater than 23 ng/mL (58 nmol/L) to lower levels. The rates of breast, colon, and rectal cancer decrease rapidly as vitamin D increases from very low values. The decrease in cancer rate then slows until vitamin D levels reach about 40 ng/mL (100 nmol/L), after which there is little further change. Comparable findings have not been reported for ovarian cancer. However, ovarian cancer may behave in a similar manner.

How vitamin D works

Vitamin D has been shown to block the growth of cancer tumors. Vitamin D3 obtained from solar UVB exposure or oral intake from food or supplements goes to the liver, where it is converted to calcidiol. From there, it goes to the kidney and other organs, where it can be converted to calcitriol as needed. Calcitriol is the hormonal version of vitamin D, which can activate vitamin D receptors and, thereby, affect the expression of many types of genes. 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

Studies compared the rates of vitamin D and breast, colon, and rectal cancers. Compared to low levels of vitamin D (below 20 ng/mL [50 nmol/L]), high levels (above 40 ng/mL [100 nmol/L]) may reduce the risk of these cancers by 15% to 25%. High levels of vitamin D may also increase survival after cancer diagnosis. These findings may also apply to ovarian cancer. Taking 1000–4000 international units (IU) (25–100 mcg)/day of vitamin D is generally required to reach blood levels of 40 ng/mL (100 nmol/L).

Vitamin D and calcium

Studies have shown that taking both vitamin D and calcium provides additional cancer protection for many types of cancer including ovarian cancer. A study in Finland found that calcium and vitamin D may act independently to reduce the risk of ovarian cancer. Calcium intake of more than 1000 mg/day from either diet or supplements is recommended.

Treatment

There are no reported studies of using vitamin D to treat ovarian cancer. However, based on studies of vitamin D and other cancers, it seems likely that vitamin D would benefit those with ovarian cancer. Those with ovarian cancer might consider taking up to 4000 IU (100 mcg)/day of vitamin D3 (cholecalciferol) to raise blood vitamin D levels to more than 40 ng/mL (100 nmol/L).

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.orgwbgrant@infionline.net The summary was reviewed by:

• Adetunji Toriola <adetunji.toriola@uta.fi></adetunji.toriola@uta.fi>

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. Arslan AA, Clendenen TV, Koenig KL, Hultdin J, Enquist K, Agren A, et al. Circulating vitamin D and risk of epithelial ovarian cancer. J Oncol. 2009;
2. Astbury A Non uniformity in cancer mortality in the USA and Australia appears to share a common pathway. 2005;
3. Bidoli E, La Vecchia C, Talamini R, Negri E, Parpinel M, Conti E, et al Micronutrients and ovarian cancer: a case-control study in Italy. Ann Oncol. 2001; 12 (11): 1589-93.
4. Boscoe FP, Schymura MJ. Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993-2000. BMC Cancer. 2006; 10 (6): 264.
5. Chen W, Clements M, Rahman B, Zhang S, Qiao Y, Armstrong BK Relationship between cancer mortality/incidence and ambient ultraviolet B irradiance in China. Cancer Causes Control. 2010 16 June [Epub ahead of print]; 16
6. Cook LS, Neilson HK, Lorenzetti DL, Lee RC. A systematic literature review of vitamin D and ovarian cancer. Am J Obstet Gynecol. 2010 March 11 [Epub ahead of print]; 203 (1): 70 e1-8.
7. Devesa SS, Grauman DJ, Blot WJ, Pennello GA, Hoover RN, Fraumeni JF Jr Atlas of Cancer Mortality in the United States, 1950-1994. 1999;
8. Freedman DM, Dosemeci M, McGlynn K Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study. Occup Environ Med. 2002; 59 (4): 257-62.
9. Garland CF, Mohr SB, Gorham ED, Grant WB, Garland FC Role of ultraviolet-B irradiance and vitamin D in the prevention of ovarian cancer. Am J Prev Med. December 2006; 31 (6): 512-514.
10. Garland, C.F. Gorham, E.D. Mohr, S.B. Garland, F.C. Vitamin D for cancer prevention: global perspective. Ann Epi. 2009; 19 (7): 468-3.
11. Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N Frequency of vitamin D (Vit D) deficiency at breast cancer (BC) diagnosis and association with risk of distant recurrence and death in a prospective cohort study of T1-3, N0-1, M0 BC. J Clin Oncol. 2008; 26 (20 Suppl):
12. Grant WB An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer. 2002; 94 (6): 1867-75.
13. Grant WB Ecologic studies of solar UV-B radiation and cancer mortality rates. Recent Results Cancer Research. 2003; 164371-7.
14. Grant WB The likely role of vitamin D from solar ultraviolet-B irradiance in increasing cancer survival. Anticancer Res. 2006; 262605-14.
15. Grant WB An ecologic study of cancer mortality rates in Spain with respect to indices of solar UV irradiance and smoking. Int J Cancer. 2007; 1201123-7.
16. Grant WB An ecological study of cancer mortality rates including indices for dietary iron and zinc. Anticancer Research. 2008; 28 (3B): 1955-63.
17. Grant WB A critical review of Vitamin D and Cancer: A report of the IARC Working Group on vitamin D. Dermato-Endocrinology. 2009a; 1 (1): 25-33.
18. Grant WB 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. Dermato-Endocrinology. 2009b; 1 (1): 17-24.
19. Grant WB Good evidence exists that solar ultraviolet-B and vitamin D reduce the risk of ovarian cancer. Am J Obstetrics Gynecol. 2010 Jun 2. [Epub ahead of print].;
20. 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):
21. Grant WB, Garland CF 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 Research. 2006; 26 (4A): 2687-99.
22. Helzlsouer KJ For the VDPP Steering committee. Overview of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epi. 2010 June 18 [Epub ahead of print]; 172 (1): 4-9.
23. Hofmann JN, Yu K, Horst RL, Hayes RB, Purdue MP Long-term variation in serum 25-hydroxyvitamin D concentration among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev. 2010; 19 (4): 927-31.
24. Ingraham, B.A. Bragdon, B. Nohe, A. Molecular basis of the potential of vitamin D to prevent cancer. Curr Med Res Opin. 2008; 24 (1): 139-49.
25. Jorde R, Sneve M, Hutchinson M, Emaus N, Figenschau Y, Grimnes G. Tracking of serum 25-hydroxyvitamin D levels during 14 years in a population-based study and during 12 months in an intervention study. Am J Epidemiol. 2010; 171 (8): 903-908.
26. Krishnan, A.V. Trump, D.L. Johnson, C.S. Feldman, D. The role of vitamin D in cancer prevention and treatment. Endocrinol Metab Clin North America. 2010; 39 (2): 401-418.
27. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007; 85 (6): 1586-91.
28. Leffell DJ, Brash DE. Sunlight and skin cancer. Sci Am. 1996; 275 (1): 52-3.
29. Lurie G, Wilkens LR, Thompson PJ, Carney ME, Palmieri RT, Pharoah PD, et al Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: Pooled analysis in five studies within the Ovarian Cancer Association Consortium. Int J Cancer. April 9 2010 [Epub ahead of print];
30. Lefkowitz ES, Garland CF Sunlight, vitamin D, and ovarian cancer mortality rates in US women. Int J Epidemiol. 1994; 23 (6): 1133-6.
31. Maia HJ, Casoy J Non-contraceptive health benefits of oral contraceptives. Eur J Contracept Reprod Health Care. March 2008; 13 (1): 17-24.
32. Ng K, Wolpin BM, Meyerhardt JA, Wu K, Chan AT, Hollis BW, et al Prospective study of predictors of vitamin D status and survival in patients with colorectal cance. Br J Cancer. Sept 2009 15; 101 (6): 916-23.
33. Peterlik, M. Grant, W.B. Cross, H.S. Calcium, vitamin D and cancer. Anticancer Res. 2009 Sept 29; 29 (9): 3687-98.
34. Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, Lichtenstein AH, Lau J, Balk EM Systematic review: Vitamin D and cardiometabolic outcomes. Ann Intern Med. 2010; 152 (5): 307-14.
35. Rice LW Hormone prevention strategies for breast, endometrial and ovarian cancers. Gynecol Oncol. 2010 May 13 [Epub ahead of print]; 118 (2): 202-7.
36. Salazar-Martinez E, Lazcano-Ponce EC, 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.
37. Toriola AT, Surcel HM, Agborsangaya C, Grankvist K, Tuohimaa P, Toniolo P, et al. Serum 25-hydroxyvitamin D and the risk of ovarian cancer. Eur J Cancer. 2010; 46 (2): 364-9.
38. Toriola AT, Surcel HM, Calypse A, Grankvist K, Luostarinen T, Lukanova A, et al 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 June 18 [Epub ahead of print];
39. Tuohimaa P, Pukkala E, Scelo G, Olsen JH, Brewster DH, Hemminki K, et al 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 May; 29 (43): 1701-1712.
40. Tworoger SS, Gate MA, Lee IM, Buring JE, Titus-Ernstoff L, Cramer D, et al Polymorphisms in the vitamin D receptor and risk of ovarian cancer in four studies. Cancer Research. March 1 2009; 69 (5): 1885-91.
41. Yin, L. Grandi, N. Raum, E. Haug, U. Arndt, V. Brenner, H. Meta-analysis: Circulating vitamin D and ovarian cancer risk. Gynecologic oncology. 2011 May 1; 121 (2): 369-75.
42. Zheng W, Danforth KN, Tworoger SS, Goodman MT, Arslan AA, Patel AV, et al Circulating 25-hydroxyvitamin D and risk of epithelial ovarian cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. 2010 June 18 [Epub ahead of print]; 172 (1): 70-80.