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A correction has been published: N Engl J Med 2006;354(10):1102.

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Volume 354:684-696 February 16, 2006 Number 7
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Calcium plus Vitamin D Supplementation and the Risk of Colorectal Cancer
Jean Wactawski-Wende, Ph.D., Jane Morley Kotchen, M.D., Garnet L. Anderson, Ph.D., Annlouise R. Assaf, Ph.D., Robert L. Brunner, Ph.D., Mary Jo O'Sullivan, M.D., Karen L. Margolis, M.D., Judith K. Ockene, Ph.D., Lawrence Phillips, M.D., Linda Pottern, Ph.D., Ross L. Prentice, Ph.D., John Robbins, M.D., Thomas E. Rohan, Ph.D., Gloria E. Sarto, M.D., Santosh Sharma, M.D., Marcia L. Stefanick, Ph.D., Linda Van Horn, Ph.D., Robert B. Wallace, M.D., Evelyn Whitlock, M.D., Tamsen Bassford, M.D., Shirley A.A. Beresford, Ph.D., Henry R. Black, M.D., Denise E. Bonds, M.D., Robert G. Brzyski, M.D., Bette Caan, Dr.P.H., Rowan T. Chlebowski, M.D., Barbara Cochrane, Ph.D., Cedric Garland, Dr.P.H., Margery Gass, M.D., Jennifer Hays, Ph.D., Gerardo Heiss, M.D., Susan L. Hendrix, D.O., Barbara V. Howard, Ph.D., Judith Hsia, M.D., F. Allan Hubbell, M.D., Rebecca D. Jackson, M.D., Karen C. Johnson, M.D., Howard Judd, M.D., Charles L. Kooperberg, Ph.D., Lewis H. Kuller, M.D., Andrea Z. LaCroix, Ph.D., Dorothy S. Lane, M.D., Robert D. Langer, M.D., Norman L. Lasser, M.D., Cora E. Lewis, M.D., Marian C. Limacher, M.D., JoAnn E. Manson, M.D., for the Women's Health Initiative Investigators

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ABSTRACT

Background Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking.

Methods We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case–control study.

Results The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics.

Conclusions Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611 [ClinicalTrials.gov] .)


Source Information

Address reprint requests to Dr. Wactawski-Wende at the Department of Social and Preventive Medicine, University at Buffalo, 270 Farber Hall, Buffalo, NY 14214, or at jww{at}buffalo.edu.

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Related Letters:

Calcium plus Vitamin D and the Risk of Colorectal Cancer
Holick M. F., Giovannucci E., Wactawski-Wende J., Anderson G. L., O'Sullivan M.
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N Engl J Med 2006; 354:2287-2288, May 25, 2006. Correspondence

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