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© 2003 Oxford University Press
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Vitamin D, Calcium Supplementation, and Colorectal Adenomas: Results of a Randomized Trial
Affiliations of authors: Department of Community and Family Medicine (MVG, MLB); Departments of Medicine and Community and Family Medicine (JAB), Dartmouth Medical School, Lebanon, NH; Department of Medicine, University of North Carolina School of Medicine, Chapel Hill (RSS); Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles (RWH); Division of Occupational and Environmental Health, University of Minnesota School of Public Health, Minneapolis (TRC); Center for Human Nutrition, University of California at Los Angeles Medical Center, Los Angeles (DH).
Correspondence to: Maria V. Grau, MD, MPH, 46 Centerra Parkway, Suite 300, Lebanon, NH 03766 (maria.grau.sepulveda{at}dartmouth.edu)
Background: Calcium and vitamin D both appear to have antineoplastic effects in the large bowel. Although these nutrients are inter-related metabolically in bone and in the normal intestine, their potential interactions in large-bowel carcinogenesis are not well understood. Methods: We assessed independent and joint effects of calcium supplementation and vitamin D status on adenoma recurrence in 803 subjects in a multi-center, placebo-controlled randomized clinical trial of calcium supplementation for the prevention of colorectal adenoma recurrence. Serum levels of 25-hydroxy [25-(OH)] vitamin D and 1,25-dihydroxy [1,25-(OH)2] vitamin D levels were determined, and the Taq I and Fok I polymorphisms in the vitamin D receptor (VDR) gene were analyzed by polymerase chain reaction. Risk ratios (RRs) for any adenoma recurrence were computed for calcium supplementation within groups defined by serum vitamin D levels and for serum vitamin D levels within treatment groups. Associations of VDR polymorphisms with recurrence risk were also evaluated. All statistical tests were two-sided. Results: Among subjects with baseline 25-(OH) vitamin D levels at or below the median (29.1 ng/mL), calcium supplementation was not associated with adenoma recurrence, whereas among those with levels above the median, calcium supplementation was associated with a reduced risk (RR = 0.71, 95 % confidence interval [CI] = 0.57 to 0.89, P for interaction = .012). Conversely, serum 25-(OH) vitamin D levels were associated with a reduced risk only among subjects receiving calcium supplements (RR per 12 ng/mL increase of vitamin D = 0.88, 95% CI = 0.77 to 0.99, P for interaction = .006). VDR polymorphisms were not related to adenoma recurrence and did not modify the associations with vitamin D or calcium. Conclusions: Calcium supplementation and vitamin D status appear to act largely together, not separately, to reduce the risk of colorectal adenoma recurrence. VDR genotype does not appear to be associated with risk.
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- Research and Public Health Implications of the Intricate Relationship Between Calcium and Vitamin D in the Prevention of Colorectal Neoplasia
- Elizabeth T. Jacobs, María Elena Martínez, and David S. Alberts
J Natl Cancer Inst 2003 95: 1736-1737.[Extract] [Full Text] [PDF]
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