Serum 25-Hydroxyvitamin D and Risks of Colon and Rectal Cancer in Finnish Men

Stephanie J. Weinstein; Kai Yu; Ronald L. Horst; Jason Ashby; Jarmo Virtamo; Demetrius Albanes


Am J Epidemiol. 2011;173(5):499-508. 

In This Article

Abstract and Introduction


Prospective investigations of circulating vitamin D concentrations suggest inverse associations with colorectal cancer risk, although inconsistencies remain and few studies have examined the impact of season. The authors conducted a prospective case-control study of 239 colon cancer cases and 192 rectal cancer cases (diagnosed in 1993–2005) and 428 controls matched on age and blood collection date within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a cohort study of Finnish male smokers. Baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations were categorized using a priori defined cutpoints of <25, 25–<37.5, 37.5–<50, 50–<75, and ≥75 nmol/L and by season-specific and season-standardized 25(OH)D quartiles. Conditional logistic regression models yielded multivariate-adjusted odds ratios for the predefined cutpoints of 0.63, 0.91, 0.73, 1.00 (referent), and 1.44 for colon cancer and 0.64, 0.58, 0.84, 1.00, and 0.76 for rectal cancer, respectively (all 95% confidence intervals included 1.00). Colon cancer risks were significantly elevated for the highest season-specific and season-standardized quartiles versus the lowest quartiles (OR = 2.11 (95% CI: 1.20, 3.69) and OR = 1.88 (95% CI: 1.07, 3.28), respectively), while rectal cancer risk estimates were null. These results provide no evidence to support an inverse association between vitamin D status and colon or rectal cancer risk; instead, they suggest a positive association for colon cancer.


In 1980, ecologic findings that colorectal cancer mortality rates in the United States were inversely associated with sunlight exposure, with vitamin D as the suggested mechanism,[1] generated interest in the relation between vitamin D and colorectal cancer. Recent reviews have concluded that low serum vitamin D concentrations are associated with increased risk of colorectal cancer;[2–4] however, not all reviews interpret the data to be consistent and convincing.[5]

Most prospective studies have supported the hypothesis of an inverse association;[6–14] however, differences exist by anatomic subsite, and not all associations are statistically significant. In addition, all but 1[12] of 9[6–14] prospective studies matched subjects on the date of blood collection, but only 4[9–12] used additional techniques to adjust for seasonal variation in vitamin D and its influence on the relation between vitamin D and colorectal cancer.

In addition to dietary and supplemental sources, vitamin D is synthesized from 7-dehydrocholesterol by the skin when exposed to solar radiation[15] and is then hydroxylated in the liver to form 25-hydroxyvitamin D (25(OH)D), the accepted biomarker of circulating vitamin D.[16] 25(OH)D is further hydroxylated in the kidney and other organs to its active form, 1,25-dihydroxyvitamin D (1,25(OH)2D).

As part of a programmatic effort to comprehensively evaluate biomarkers of vitamin D and cancer, we conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a cohort study of male smokers in Finland. Multiple approaches were used to address the issues related to seasonal variation in 25(OH)D concentrations.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.