Calcium plus vitamin D supplementation and the risk of colorectal cancer
Department of Medicine, Division of Preventive and Behavioral Medicine
Adenocarcinoma; Aged; Calcium; Calcium Carbonate; Colonic Polyps; Colorectal Neoplasms; Double-Blind Method; Drug Combinations; Female; Follow-Up Studies; Humans; Incidence; Middle Aged; Postmenopause; Proportional Hazards Models; Vitamin D
Life Sciences | Medicine and Health Sciences | Women's Studies
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 [corrected] 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.).
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Citation: N Engl J Med. 2006 Feb 16;354(7):684-96. Link to article on publisher's site
Wactawski-Wende, Jean; Kotchen, Jane Morley; Anderson, Garnet L.; Assaf, Annlouise R.; Brunner, Robert L.; O'Sullivan, Mary Jo; Margolis, Karen L.; Ockene, Judith K.; Phillips, Lawrence; Pottern, Linda; Prentice, Ross L.; Robbins, John A.; Rohan, Thomas E.; Sarto, Gloria E.; Sharma, Santosh; Stefanick, Marcia L.; Van Horn, Linda; Wallace, Robert B.; Whitlock, Evelyn; Bassford, Tamsen; Beresford, Shirley A. A.; Black, Henry R.; Bonds, Denise E.; Brzyski, Robert G.; Caan, Bette J.; Chlebowski, Rowan T.; Cochrane, Barbara B.; Garland, Cedric; Gass, Margery; Hays, Jennifer; Heiss, Gerardo; Hendrix, Susan L.; Howard, Barbara V.; Hsia, Judith; Hubbell, F. Allan; Jackson, Rebecca D.; Johnson, Karen C.; Judd, Howard; Kooperberg, Charles L.; Kuller, Lewis H.; LaCroix, Andrea Z.; Lane, Dorothy S.; Langer, Robert D.; Lasser, Norman L.; Lewis, Cora E.; Limacher, Marian C.; and Manson, JoAnn E., "Calcium plus vitamin D supplementation and the risk of colorectal cancer" (2006). Women’s Health Research Faculty Publications. 437.