Colorectal cancer Introduction

 Lower levels of vitamin D are associated with higher risk of colorectal cancer.

Colorectal cancer is cancer of the colon (bowel) or rectum. It is one of the most common types of cancer in Western developed countries.

Colorectal cancer is the cancer for which the evidence of a beneficial role of vitamin D is strongest. There is ample evidence from numerous ecological (geographical), cross-sectional (pictures in time), prospective (looking forward), and case-control studies (looking forward with a control group), meta-analyses (combination) of such studies, and laboratory investigations of mechanisms.

The meta-analyses of nested case-control studies finds a 25% reduced incidence rate for 45 ng/mL vs. 25 ng/mL serum 25-hydroxyvitamin D [25(OH)D] level. Survival rates after diagnosis are higher for those with higher serum 25(OH)D levels at time of diagnosis.

Colorectal cancer is a common type of cancer in Western developed countries. Important risk factors for colorectal cancer include diets high in animal products1, smoking2, and alcohol consumption3. When diets in countries with traditional diets low in animal products, colorectal cancer rates rise after introduction of more animal products with about a 20-year lag after the change4.

Lower rates of colorectal cancer are seen in areas that have more sunlight.

The UVB-vitamin D-cancer hypothesis was originally proposed by the brothers Cedric Garland and Frank Garland5 after seeing early maps from the Atlas of Cancer Mortality in the United States6 and noticing that colon cancer mortality rates in the southwest were much lower than in the northeast, about half as much. They also noted that solar radiation doses were much higher in the southwest than in the northeast, and based the hypothesis on the fact that the most important physiological effect of solar radiation is production of vitamin D. They followed that paper with one showing that dietary vitamin D and calcium were inversely correlated with colorectal cancer7 and that prediagnostic serum 25(OH)D was also inversely correlated with colon cancer incidence8.

Colorectal cancer is the cancer with the strongest evidence for a beneficial role of solar ultraviolet-B (UVB) irradiance and vitamin D in reducing the risk. The International Agency for Research on Cancer (IARC) concluded that it was the only cancer with strong evidence9.

A review by Giovannucci10 concluded that the entire body of evidence is supportive of a causal association between vitamin D status and risk of colorectal cancer. Grant11 also showed that the UVB-vitamin D-cancer hypothesis satisfies Hill’s criteria for causality in a biological system for several cancers in general and colorectal cancer in particular. These criteria include strength of association, determining a dose-response relationship, repeating the finding in several diverse populations, finding mechanisms, and experimental verification. Not all criteria need be satisfied, but the more that are, the better.

Page last edited: 22 August 2011

References

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  7. Garland, C. Shekelle, R. B. Barrett-Connor, E. Criqui, M. H. Rossof, A. H. Paul, O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet. 1985 Feb 9; 1 (8424): 307-9.
  8. Garland, C. F. Comstock, G. W. Garland, F. C. Helsing, K. J. Shaw, E. K. Gorham, E. D. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet. 1989 Nov 18; 2 (8673): 1176-8.
  9. IARC Vitamin D and Cancer. IARC Working Group Reports. 2008; 5465 pp.
  10. Giovannucci, E. Epidemiology of vitamin D and colorectal cancer: casual or causal link?. J Steroid Biochem Mol Biol. 2010 Jul; 121 (1-2): 349-54.
  11. 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. Dermato-Endocrinology. 2009; 1 (1): 14-21.