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


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