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Plasma 1,25-Dihydroxy- and 25-Hydroxyvitamin D and Adenomatous Polyps of the Distal Colorectum¹

Departments of Epidemiology [E. A. P., S. E. H., G. A. C., D. J. H., E. G.] and Nutrition [E. A. P., D. J. H., E. G.], Harvard School of Public Health, Boston, Massachussetts 02115; Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham & Women’s Hospital [S. E. H., G. A. C., D. J. H., F. E. S., E. G.], Boston, Massachussetts 02115; and Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425 [B. W. H.]

1,25-dihydroxyvitamin D [1,25(OH)₂D] inhibits proliferation and promotes differentiation of human colon cancer cell lines. Epidemiological findings, although not entirely consistent, suggest an inverse relationship between vitamin D intake and colorectal cancer and adenoma, colorectal cancer precursor lesions. We evaluated the relationship of plasma 1,25(OH)₂D and 25-hydroxyvitamin D [25(OH)D] with distal colorectal adenoma among 326 matched case and control pairs (nested in the prospective Nurses’ Health Study), who provided blood in 1989–1990 and who underwent endoscopy in 1989–1996. Plasma vitamin D metabolite concentrations were determined blindly by RIA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multiple conditional logistic regression models. Mean plasma 1,25(OH)₂D and 25(OH)D levels did not significantly differ (P = 0.3 and 0.7, respectively) between cases (31.6 ± 8.4 pg/ml and 26.4 ± 10.6 ng/ml, respectively) and controls (32.2 ± 8.6 pg/ml and 26.8 ± 10.2 ng/ml, respectively). However, women whose plasma 1,25(OH)₂D concentration was below 26.0 pg/ml (a level typically considered to be below normal) were at increased risk of distal colorectal adenoma (OR, 1.58; 95% CI, 1.03–2.40). Compared with the lowest 1,25(OH)₂D quartile, women in the second (OR, 0.64; 95% CI, 0.41–1.02), third (OR, 0.80; 95% CI, 0.50–1.30), or upper (OR, 0.71; 95% CI, 0.43–1.15) quartiles were at a statistically nonsignificant lower risk of adenoma. The relationship was stronger for large/villous adenoma and among those with consistent vitamin D intake over the 10 years prior to blood draw. Compared with women in the lowest quartile, for plasma 25(OH)D, women in the second (OR, 0.64; 95% CI, 0.41–1.00) and third (OR, 0.58; 95% CI, 0.36–0.95) quartiles were at a statistically significantly lower risk of distal colorectal adenoma, but there was no difference in risk in the top quartile (OR, 1.04; 95% CI, 0.66–1.66). We conclude that women who have low levels of circulating 1,25(OH)₂D may be at higher risk of distal colorectal adenomas, but additional study is warranted.

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