Calcium plus Vitamin D Supplementation and the Risk of Colorectal Cancer

doi:10.1056/NEJMoa055222

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

Volume 354:684-696		February 16, 2006		Number 7

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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by Forman, M. R.

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ABSTRACT

Background Higher intake of calcium and vitamin D has been associatedwith a reduced risk of colorectal cancer in epidemiologic studiesand polyp recurrence in polyp-prevention trials. However, randomized-trialevidence that calcium with vitamin D supplementation is beneficialin the primary prevention of colorectal cancer is lacking.

Methods We conducted a randomized, double-blind, placebo-controlledtrial involving 36,282 postmenopausal women from 40 Women'sHealth Initiative centers: 18,176 women received 500 mg of elementalcalcium as calcium carbonate with 200 IU of vitamin D₃ twicedaily (1000 mg of elemental calcium and 400 IU of vitamin D₃)and 18,106 received a matching placebo for an average of 7.0years. The incidence of pathologically confirmed colorectalcancer was the designated secondary outcome. Baseline levelsof serum 25-hydroxyvitamin D were assessed in a nested case–controlstudy.

Results The incidence of invasive colorectal cancer did notdiffer significantly between women assigned to calcium plusvitamin D supplementation and those assigned to placebo (168and 154 cases; hazard ratio, 1.08; 95 percent confidence interval,0.86 to 1.34; P=0.51), and the tumor characteristics were similarin the two groups. The frequency of colorectal-cancer screeningand abdominal symptoms was similar in the two groups. Therewere no significant treatment interactions with baseline characteristics.

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

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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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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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