Colorectal cancerVitamin D levels

Adenomas are precursors to cancer, and colorectal adenomas (called polyps if protruding) are often discovered through screening for colorectal cancer via colonoscopy or sigmiodoscopy.

In a study in Japan of men about to retire, for those whose blood was taken during the winter season (November-April), the prevalence odds of colorectal adenomas for the highest versus lowest quartile of 25(OH)D was statistically significantly decreased [odds ratio (OR) = 0.58; 95% CI = 0.34-0.99]. During the summer season (May-October), higher levels of 25(OH)D were associated with an increased odds of small, but not large, adenomas1.

In a pooled analysis of primary data from three colonoscopy-based case-control studies conducted in Minnesota, North Carolina, and South Carolina between 1991 and 2002, higher circulating 25(OH)D(3) concentrations were statistically significantly associated with decreased colorectal adenoma risk (highest vs. lowest quartile OR = 0.59, 95% CI: 0.41, 0.84). The observed inverse association was stronger among participants who used nonsteroidal antiinflammatory drugs regularly (highest vs. lowest quartile odds ratio = 0.33, 95% confidence interval: 0.19, 0.56)2.

The results from the various studies are combined, generally in a meta-analysis by examining the change in incidence with respect to midpoints of serum 25(OH)D levels for four or five “quantiles” for each study. 

A meta-analysis composed of 17 epidemiologic studies published before December 2007 was done to examine the association between circulating 25(OH)D, vitamin D intake, and colorectal adenomas. Adenomas are benign, non-cancerous tumors. Circulating 25(OH)D was inversely associated with risk of colorectal adenomas: the OR was 0.70 (95% CI, 0.56-0.87) for high versus low circulating 25(OH)D. The highest quintile of vitamin D intake was associated with an 11% marginally decreased risk of colorectal adenomas compared with low vitamin D intake (OR, 0.89; 95% CI, 0.78-1.02). For recurrent adenomas, there was a decreased risk of 12% (95% CI, 0.72-1.07) among individuals with high versus low vitamin D intake. The inverse associations appeared stronger for advanced adenoma [OR, 0.64; 95% CI, 0.45-0.90 for serum 25(OH)D and OR, 0.77; 95% CI, 0.63-0.95 for vitamin D intake], but the number of studies was small3.

A subsequent meta-analysis of colorectal adenoma (CRA) incidence or recurrence found “summary odd ratios (95% confidence intervals) regarding incident and recurrent CRA, and both outcomes combined were 0.82 (0.69-0.97), 0.87 (0.56-1.35), and 0.84 (0.72-0.97), respectively, for an increase of 25(OH)D by 20ng/ml”4. 

These results indicate that the beneficial effect of vitamin D becomes stronger as adenomas become more like cancers. In an ecological study, the inverse correlation of colorectal cancer with solar UVB was stronger for mortality rate than incidence rate5. 

There have been several prospective nested case-control studies that looked at colorectal cancer incidence as a function of prediagnostic serum 25(OH)D6 7 8 9 10 11. There is also one cross-sectional study12: “Colorectal cancer mortality was inversely related to serum 25(OH)D level, with levels 80 nmol/L or higher associated with a 72% risk reduction (95% confidence interval = 32% to 89%) compared with lower than 50 nmol/L, P(trend) = .02.”

Three recent meta-analyses found a 30-40% reduced incidence rate for a 20 ng/mL increase in serum 25(OH)D level above the lowest level of 10-20 ng/mL13 14 15. Increasing serum 25(OH)D level from 25 ng/mL common to White Americans16 to 45 ng/mL would reduce the incidence of colorectal cancer by 25%14.

There was also a cohort study on the basis of a vitamin D index based on oral intake and solar UVB irradiance, finding a 40% (95% CI, 20-60%) reduced risk of colorectal cancer for 10 ng/mL increase in serum 25(OH)D level17.

A European study found that vitamin A (retinol) reduced the effectiveness of vitamin D in reducing the risk of cancer7. Cod liver oil is an important source of vitamin D in Nordic countries and contains a significant amount of vitamin A. 

Oral intake of vitamin D

Several studies also investigated the incidence of colorectal cancer with respect to oral intake of vitamin D from diet and supplements. A case-control study in Italy looking at oral intake at the time of diagnosis found a statistically significant inverse correlation for colorectal cancer for women but not men18. A possible reason for the difference is that men are likely to produce more vitamin D from sunlight than females. Another case-control study in Italy also found a statistically significant inverse correlation between vitamin D intake and incidence of colon cancer19.

A study in Japan found a nearly statistically significant inverse correlation between vitamin D intake and colorectal cancer incidence for those who were sedentary and spent most of their time indoors, but a small statistically insignificant inverse correlation for those who spent more than 120 min/wk in outdoor activities20.

A case-control study in the United States found a statistically significant inverse correlation for high vitamin D intake for those with some vitamin D receptors (VDRs) compared to those with low vitamin D intake and other VDRs21.

There have also been a number of nested case-control studies of colorectal cancer with respect to oral intake of vitamin D. Two with follow-up times of 5 and 19 years found statistically significant inverse correlations22 23. One with a 10-year follow-up period found a statistically significant increased risk24, and one with a 6.9-year follow-up period found a statistically insignificant inverse correlation25.

Page last edited: 22 August 2011

References

  1. Takahashi, R. Mizoue, T. Otake, T. Fukumoto, J. Tajima, O. Tabata, S. Abe, H. Ohnaka, K. Kono, S. Circulating vitamin D and colorectal adenomas in Japanese men. Cancer Sci. 2010 Jul; 101 (7): 1695-700.
  2. Fedirko, V. Bostick, R. M. Goodman, M. Flanders, W. D. Gross, M. D. Blood 25-hydroxyvitamin D3 concentrations and incident sporadic colorectal adenoma risk: a pooled case-control study. Am J Epidemiol. 2010 Sep 1; 172 (5): 489-500.
  3. Wei, M. Y. Garland, C. F. Gorham, E. D. Mohr, S. B. Giovannucci, E. Vitamin D and prevention of colorectal adenoma: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2008 Nov; 17 (11): 2958-69.
  4. Yin, L. Grandi, N. Raum, E. Haug, U. Arndt, V. Brenner, H. Meta-analysis: Serum vitamin D and colorectal adenoma risk. Preventive medicine. 2011 Jun 13;
  5. 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.
  6. Feskanich, D. Ma, J. Fuchs, C. S. Kirkner, G. J. Hankinson, S. E. Hollis, B. W. Giovannucci, E. L. Plasma vitamin D metabolites and risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev. 2004 Sep; 13 (9): 1502-8.
  7. Jenab, M. et al Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case-control study. BMJ. 2010; 340b5500.
  8. Tangrea, J. Helzlsouer, K. Pietinen, P. Taylor, P. Hollis, B. Virtamo, J. Albanes, D. Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal cancer in Finnish men. Cancer Causes Control. 1997 Jul; 8 (4): 615-25.
  9. Wactawski-Wende, J. Kotchen, J. M. Anderson, G. L. Assaf, A. R. Brunner, R. L. O'Sullivan, M. J. Margolis, K. L. Ockene, J. K. Phillips, L. Pottern, L. Prentice, R. L. Robbins, J. Rohan, T. E. Sarto, G. E. Sharma, S. Stefanick, M. L. Van Horn, L. Wallace, R. B. Whitlock, E. Bassford, T. Beresford, S. A. Black, H. R. Bonds, D. E. Brzyski, R. G. Caan, B. Chlebowski, R. T. Cochrane, B. Garland, C. Gass, M. Hays, J. Heiss, G. Hendrix, S. L. Howard, B. V. Hsia, J. Hubbell, F. A. Jackson, R. D. Johnson, K. C. Judd, H. Kooperberg, C. L. Kuller, L. H. LaCroix, A. Z. Lane, D. S. Langer, R. D. Lasser, N. L. Lewis, C. E. Limacher, M. C. Manson, J. E. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006 Feb 16; 354 (7): 684-96.
  10. Woolcott, C. G. Wilkens, L. R. Nomura, A. M. Horst, R. L. Goodman, M. T. Murphy, S. P. Henderson, B. E. Kolonel, L. N. Le Marchand, L. Plasma 25-hydroxyvitamin D levels and the risk of colorectal cancer: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev. 2010 Jan; 19 (1): 130-4.
  11. Wu, K. Feskanich, D. Fuchs, C. S. Willett, W. C. Hollis, B. W. Giovannucci, E. L. A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. J Natl Cancer Inst. 2007 Jul 18; 99 (14): 1120-9.
  12. Freedman, D. M. Looker, A. C. Chang, S. C. Graubard, B. I. Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst. 2007 Nov 7; 99 (21): 1594-602.
  13. 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;
  14. 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;
  15. 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.
  16. 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.
  17. 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.
  18. La Vecchia, C. Braga, C. Negri, E. Franceschi, S. Russo, A. Conti, E. Falcini, F. Giacosa, A. Montella, M. Decarli, A. Intake of selected micronutrients and risk of colorectal cancer. International journal of cancer. Journal international du cancer. 1997 Nov 14; 73 (4): 525-30.
  19. Lipworth, L. Bender, T. J. Rossi, M. Bosetti, C. Negri, E. Talamini, R. Giacosa, A. Franceschi, S. McLaughlin, J. K. La Vecchia, C. Dietary vitamin D intake and cancers of the colon and rectum: a case-control study in Italy. Nutr Cancer. 2009; 61 (1): 70-5.
  20. Mizoue, T. Kimura, Y. Toyomura, K. Nagano, J. Kono, S. Mibu, R. Tanaka, M. Kakeji, Y. Maehara, Y. Okamura, T. Ikejiri, K. Futami, K. Yasunami, Y. Maekawa, T. Takenaka, K. Ichimiya, H. Imaizumi, N. Calcium, dairy foods, vitamin D, and colorectal cancer risk: the Fukuoka Colorectal Cancer Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2008 Oct; 17 (10): 2800-7.
  21. Slattery, M. L. Neuhausen, S. L. Hoffman, M. Caan, B. Curtin, K. Ma, K. N. Samowitz, W. Dietary calcium, vitamin D, VDR genotypes and colorectal cancer. International journal of cancer. Journal international du cancer. 2004 Sep 20; 111 (5): 750-6.
  22. 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.
  23. McCullough, M. L. Robertson, A. S. Rodriguez, C. Jacobs, E. J. Chao, A. Carolyn, J. Calle, E. E. Willett, W. C. Thun, M. J. Calcium, vitamin D, dairy products, and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States). Cancer Causes Control. 2003 Feb; 14 (1): 1-12.
  24. Lin, J. Zhang, S. M. Cook, N. R. Manson, J. E. Lee, I. M. Buring, J. E. Intakes of calcium and vitamin D and risk of colorectal cancer in women. American journal of epidemiology. 2005 Apr 15; 161 (8): 755-64.
  25. Kesse, E. Boutron-Ruault, M. C. Norat, T. Riboli, E. Clavel-Chapelon, F. Dietary calcium, phosphorus, vitamin D, dairy products and the risk of colorectal adenoma and cancer among French women of the E3N-EPIC prospective study. International journal of cancer. Journal international du cancer. 2005 Oct 20; 117 (1): 137-44.