Epidemiological studies have suggested a reduced risk of several cancers associated with high vitamin D status. We performed a systematic review with meta-analyses of observational studies of serum 25-hydroxyvitamin D level and colorectal, breast and prostate cancer and colonic adenoma. The literature of December 2009 was searched without language restriction. The meta-regression analysis was done to compute dose-response effects. Because in case-control studies, serum 25-hydroxyvitamin D level is measured after the diagnosis of cancer, separate analyses for case-control and prospective studies were done. We identified 35 independent studies. The seven studies on colorectal adenomas were heterogeneous in terms of endpoint and control for major confounding factors, and we did not perform a meta-analysis of these data. The summary relative risk (SRR) and (95% confidence interval) for a 10 ng/ml increase in serum 25-hydroxyvitamin D was 0.85 (0.79; 0.91) for colorectal cancer (2,630 cases in 9 studies); 0.89 (0.81;0.98) for breast cancer (6,175 cases in 10 studies); and 0.99 (0.95;1.03) for prostate cancer (3,956 cases in 11 studies). For breast cancer, case-control studies (3,030 cases) had major limitations and obtained SRR of 0.83 (0.79; 0.87) whereas SRR of prospective studies (3,145 cases) was 0.97 (0.92; 1.03). For colorectal and breast cancer, differences between cases and controls in the season of blood draw or in overweight/obesity or physical inactivity could not explain the results. In conclusion, a consistent inverse relationship between serum 25-hydroxyvitamin D levels and colorectal cancer was found. No association was found for breast and prostate cancer.Vitamin D can inhibit cell proliferation and promote apoptosis in vitro, and several tissues can locally produce the physiologically active form of vitamin D, 1a,25-dihydroxyvitamin D, which has anticarcinogenic properties.1 In addition, these tissues express the vitamin D receptor (VDR) that enables cellular action of the 1a,25-dihydroxyvitamin D. These basic research findings have strengthened the credibility of the hypothesis largely derived from ecological studies in the USA by which a higher vitamin D status would be associated with a lower risk of cancer.
2The 25-hydroxyvitamin D is the precursor of the physiologically active 1a,25-dihydroxyvitamin. The serum level of 25-hydroxyvitamin D is a result of skin exposure to sunlight, total vitamin D intake, and other factors such as age and skin pigmentation. Serum levels vary with season, with the highest levels in summer and autumn. 25-hydroxyvitamin D has a half-life in the circulatory system of about 2-3 weeks.
3In contrast, serum 1a,25-dihydroxyvitamin D is tightly biochemically regulated, except in situations of extreme deficiency, in keeping with its role in calcium homeostasis. It has a circulating half-time of 5-15 hr and exhibits little seasonal variability.3,4 For these reasons, the serum 25-hydroxyvitamin D is considered as reflecting the vitamin D status better than the serum 1a,25-dihy...