Vitamin D and Colorectal Cancer Prevention

Abstracted February 18, 2010 by Marcia J. Egles, MD from Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case-control study by Mazda Jenab et al in BMJ, 21 January 2010.

KEY WORDS: vitamin D, cancer

A large European case-control study, recently reported in the British Medical Journal (1), links low vitamin D levels with a higher risk of colorectal cancer. The study is part of EPIC, the European Prospective Investigation into Cancer and Nutrition which involved 520,000 participants from ten western European countries (2). Between 1992 and 1998, personal histories and blood samples were collected from men and women of the general population aged 30 to 76 years (average age 58). During a follow-up period averaging 3.8 years, 1248 persons were diagnosed with colorectal cancer. These cases were matched with similar persons in the study who did not have cancer. Their characteristics including their vitamin D levels from the blood samples at the start of the study were compared (1).

The vitamin D levels (serum 25-(OH)D) showed a strong inverse dose-response associated with a higher risk of colorectal cancer (p for trend less than 0.001). That is, lower levels of vitamin D were associated with higher risk of colorectal cancer. (A serum 25-hydroxyvitamin D level of less than 50 nanomoles per liter is generally considered deficient.) When compared to a vitamin D level of 50- 75 nanomoles per liter, those with vitamin D levels lower than 25 nanomoles per liter had an incident rate ratio* of 1.32 ( 95% confidence interval 0.87-2.01). Those with vitamin D levels 25 to 49 nanomoles per liter had an incident rate ratio of 1.28. (95% confidence interval, 1.05 to 1.56). Those with vitamin D levels 75.5 to 99 nanomoles per liter showed an incident rate ratio of 0.88 (95% confidence interval 0.68 to 1.13).

When the results were analyzed by “quintiles”, dividing the populations into fifths, a similar pattern emerged. Those in the highest quintile, the highest fifth of vitamin D levels, had a 40% lower risk of colorectal cancer than those in the lowest quintile (p less than 0.001). The findings in this study did not significantly vary between men compared to women, nor was there any effect based on season or month of the blood collection.

Also noted in the study, those with the lowest vitamin D levels who also reported the highest alcohol consumptions had among the highest cancer risk in the study. The incident rate ratio for this subgroup was 1.46 (95% confidence interval 1.16 to 1.83). In the same study, when vitamin D dietary intakes were considered, no associations were found with colorectal cancer risk. This was not an unexpected result as diet surveys do not account for vitamin D obtained by sunlight exposure.

The results of this EPIC study of vitamin D blood levels may help clarify some previous studies which report no association between vitamin D and colorectal cancer (3). The Women’s Health Initiative Study, a major clinical trial (4), showed no benefits of supplementation (1000mg per day calcium plus 400 I.U. per day of vitamin D). However, both the EPIC study and the Women’s Health Initiative Study reported similar findings with vitamin D blood levels. The Women’s Health Initiative Study also found that those who had a baseline serum 25-hydroxyvitamin D level of less than 30 nanomoles per liter had a 253% increase in the risk of colorectal cancer over a follow-up of 8 years (5).

The researchers from the EPIC case-control study stressed that additional randomized clinical trials are needed to test whether or not increases in 25-hydroxyvitamin D concentrations are effective in reducing colorectal cancer risk (1).

*incident rate ratio- The higher the ratio is over 1, the higher the risk. If the ratio is less than 1, the risk is reduced.

REFERENCES:

1. Jenab, Mazda et al. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study BMJ Published 21 January 2010, doi:10.1136/bmj.b5500

2. Riboli E, Hunt KJ, Slimani N, Ferrari P, Norat T, Fahey M, et al. European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 2002;5:1113-24

3. Feskanich D, et al. Plasma vitamin D metabolites and the risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Pre 2004: 13: 1502-8.

4. Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’Sullivan MJ, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006;354:684-96.I

5. Holick MF. Calcium plus vitamin D and the risk of colorectal cancer. N Engl J Med 2006: 354: 2287-8