Vitamin D and Gastric Cancer

Gastric cancer

Stomach (gastric) cancer is a moderately important cause of disease and death. In the United States each year, it affects about 21 thousand people and kills approximately 11 thousand.

Risk factors

Of the many risk factors associated with gastric cancer, the most important include:

• Helicobacter pylori bacteria infection is the leading cause of stomach cancer. It can be eliminated with antibiotics.
• Smoking: Smoking is associated with risk of stomach cancer.
• Salt and salted food intake is associated with stomach cancer.
• Exercise is protective against stomach cancer.
• Obesity: Obesity is a weak risk for stomach cancer.
• Dried fish, meat, and simple carbohydrates such as sugar are associated with increased risk of stomach cancer.
• Diet-eating fruits and vegetables and high fiber grain products reduces the risk of stomach cancer.

Sunlight exposure and stomach cancer risk

Sunlight has a direct effect on reducing risk of many types of cancer. The shortwave ultraviolet portion of sunlight, ultraviolet-B (UVB), stimulates the body to produce vitamin D, which protects against cancer. Many ecological studies (comparison of disease rates where people live to disease risk factor values) have found lower rates of stomach cancer with respect to higher amounts of ultraviolet-B (UVB) from sunlight. Such studies were conducted in China, Japan, and the United States.

Vitamin D and stomach cancer

Vitamin D levels

No study has reported reduced risk of stomach cancer with higher vitamin D blood levels. In fact, observational studies in China found an increased risk of stomach cancer associated with higher vitamin D blood levels. This finding may be explained by some risk factors not included in the study. The rates of breast, colon, and rectal cancer decrease rapidly as vitamin D levels increase from very low levels [less than 10 ng/ml (25 nmol/] out to 20-30 ng/ml, then decreases at a slower rate until levels reach about 50 ng/ml (150 nmol/l). No comparable findings have been reported for other types of cancer. However, it is assumed that they behave in a similar manner.

How vitamin D works

Vitamin D has been shown to block the growth of cancer tumors. Calcitriol, an active form of vitamin D, is produced by the body from vitamin D processed by the liver. 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 many types of cancer and reduced tumor growth. Based on studies of breast, colon, and rectal cancer, vitamin D levels of 40–60 ng/mL (100–150 nmol/L) may reduce the risk of cancer. Taking 1000–4000 international units (IU) (25–100 mcg)/day raises vitamin D levels to those amounts for most people.

Vitamin D and calcium

There is evidence that calcium is also associated with reduced risk of stomach cancer.

Treatment

People with higher vitamin D levels at time of cancer diagnosis often have a higher survival rate. This has been verified for people with breast, colorectal, lung, and prostate cancer; non-Hodgkin’s lymphoma; and melanoma. These studies suggest that increasing vitamin D levels after cancer diagnosis may improve chances of survival. Some cancer treatment centers are now giving at least 5000 IU (125 mcg)/day vitamin D3 (calcitriol) 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:

• Tetsuya Mizoue mizoue@ri.ncgm.go.jp

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. Abnet, C. C. Chen, Y. Chow, W. H. Gao, Y. T. Helzlsouer, K. J. Le Marchand, L. McCullough, M. L. Shikany, J. M. Virtamo, J. Weinstein, S. J. Xiang, Y. B. Yu, K. Zheng, W. Albanes, D. Arslan, A. A. Campbell, D. S. Campbell, P. T. Hayes, R. B. Horst, R. L. Kolonel, L. N. Nomura, A. M. Purdue, M. P. Snyder, K. Shu, X. O. Circulating 25-hydroxyvitamin D and risk of esophageal and gastric cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. 2010 Jul 1; 172 (1): 94-106.
2. Astbury, A. Non uniformity in cancer mortality in the USA and Australia appears to share a common origin. 2005; (TRI-PP-05-01):
3. Blaser, M. J. Chyou, P. H. Nomura, A. Age at establishment of Helicobacter pylori infection and gastric carcinoma, gastric ulcer, and duodenal ulcer risk. Cancer Res. 1995 Feb 1; 55 (3): 562-5.
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. Brown, L. M. Devesa, S. S. Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N Am. 2002 Apr; 11 (2): 235-56.
6. Chen, W. Clements, M. Rahman, B. Zhang, S. Qiao, Y. Armstrong, B. K. Relationship between cancer mortality/incidence and ambient ultraviolet B irradiance in China. Cancer Causes Control. 2010 Jun 16;
7. Chen, W. Dawsey, S. M. Qiao, Y. L. Mark, S. D. Dong, Z. W. Taylor, P. R. Zhao, P. Abnet, C. C. Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers. Br J Cancer. 2007 Jul 2; 97 (1): 123-8.
8. Compare, D. Rocco, A. Nardone, G. Risk factors in gastric cancer. Eur Rev Med Pharmacol Sci. 2010 Apr; 14 (4): 302-8.
9. Devesa, S. S. Grauman, D. J. Blot, W. J. Pennello, G. A. Hoover, R. N. Fraumeni, J. F. Jr. Atlas of Cancer Mortality in the United States, 1950-1994. NIH Publication No. 99-4564. 1999 April 17, 2010;
10. Garland, C. F. Gorham, E. D. Mohr, S. B. Garland, F. C. Vitamin D for cancer prevention: global perspective. Ann Epidemiol. 2009 Jul; 19 (7): 468-83.
11. Ginde, A. A. Liu, M. C. Camargo, C. A., Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009 Mar 23; 169 (6): 626-32.
12. 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.
13. Gombart, A. F. Luong, Q. T. Koeffler, H. P. Vitamin D compounds: activity against microbes and cancer. Anticancer Res. 2006 Jul-Aug; 26 (4A): 2531-42.
14. Goodwin, P. J. et al. 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 May; 20511.
15. 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.
16. Grant, W. B. Lower vitamin-D production from solar ultraviolet-B irradiance may explain some differences in cancer survival rates. J Natl Med Assoc. 2006 Mar; 98 (3): 357-64.
17. 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.
18. Grant, W. B. Does solar ultraviolet irradiation affect cancer mortality rates in China?. Asian Pac J Cancer Prev. 2007 Apr-Jun; 8 (2): 236-42.
19. Grant, W. B. An ecological study of cancer mortality rates including indices for dietary iron and zinc. Anticancer Res. 2008 May-Jun; 28 (3B): 1955-63.
20. Grant, W. B. A critical review of Vitamin D and cancer: A report of the IARC Working Group on vitamin D. Dermato-endocrinology. 2009; 1 (1): 25-33.
21. 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.
22. 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.
23. 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):
24. 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;
25. Hase, K. Murakami, M. Iimura, M. Cole, S. P. Horibe, Y. Ohtake, T. Obonyo, M. Gallo, R. L. Eckmann, L. Kagnoff, M. F. Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. Gastroenterology. 2003 Dec; 125 (6): 1613-25.
26. Hellstrom, P. M. This year’s Nobel Prize to gastroenterology: Robin Warren and Barry Marshall awarded for their discovery of Helicobacter pylori as pathogen in the gastrointestinal tract. World J Gastroenterol. 2006 May 21; 12 (19): 3126-7.
27. 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.
28. Hofmann, J. N. Yu, K. Horst, R. L. Hayes, R. B. Purdue, M. P. 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 Apr; 19 (4): 927-31.
29. Ingraham, B. A. Bragdon, B. Nohe, A. Molecular basis of the potential of vitamin D to prevent cancer. Curr Med Res Opin. 2008 Jan; 24 (1): 139-49.
30. 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 Apr 15; 171 (8): 903-8.
31. 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 Am. 2010 Jun; 39 (2): 401-18, table of contents.
32. 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.
33. Leffell, D. J. Brash, D. E. Sunlight and skin cancer. Sci Am. 1996 Jul; 275 (1): 52-3, 56-9.
34. Marshall, B. J. Warren, J. R. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984 Jun 16; 1 (8390): 1311-5.
35. Mizoue, T. Ecological study of solar radiation and cancer mortality in Japan. Health Phys. 2004 Nov; 87 (5): 532-8.
36. Nasri, H. Baradaran, A. The influence of serum 25-hydroxy vitamin D levels on Helicobacter Pylori Infections in patients with end-stage renal failure on regular hemodialysis. Saudi J Kidney Dis Transpl. 2007 Jun; 18 (2): 215-9.
37. Ng, K. Wolpin, B. M. Meyerhardt, J. A. Wu, K. Chan, A. T. Hollis, B. W. Giovannucci, E. L. Stampfer, M. J. Willett, W. C. Fuchs, C. S. Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer. Br J Cancer. 2009 Sep 15; 101 (6): 916-23.
38. Peterlik, M. Grant, W. B. Cross, H. S. Calcium, vitamin D and cancer. Anticancer Res. 2009 Sep; 29 (9): 3687-98.
39. Seidler, A. Hammer, G. P. Husmann, G. Konig, J. Krtschil, A. Schmidtmann, I. Blettner, M. Cancer risk among residents of Rhineland-Palatinate winegrowing communities: a cancer-registry based ecological study. J Occup Med Toxicol. 2008; 312.
40. Shanafelt, T. D. Drake, M. T. Maurer, M. J. Allmer, C. Rabe, K. G. Slager, S. L. Weiner, G. J. Call, T. G. Link, B. K. Zent, C. S. Kay, N. E. Hanson, C. A. Witzig, T. E. Cerhan, J. R. Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia (CLL). Blood. 2010 Nov 3;
41. Travis, P. B. Goodman, K. J. O’Rourke, K. M. Groves, F. D. Sinha, D. Nicholas, J. S. VanDerslice, J. Lackland, D. Mena, K. D. The association of drinking water quality and sewage disposal with Helicobacter pylori incidence in infants: the potential role of water-borne transmission. J Water Health. 2010 Mar; 8 (1): 192-203.
42. 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.
43. Yang, C. Y. Cheng, M. F. Tsai, S. S. Hsieh, Y. L. Calcium, magnesium, and nitrate in drinking water and gastric cancer mortality. Jpn J Cancer Res. 1998 Feb; 89 (2): 124-30.